DOI 10.1515/hsz-2013-0133 Biol. Chem. 2013; 394(7): 845–855
Review
Ü lo Maiv ä li * , Anton Paier and Tanel Tenson
When stable RNA becomes unstable: the degradation of ribosomes in bacteria and beyond Abstract: This review takes a comparative look at the
various scenarios where ribosomes are degraded in bac-
teria and eukaryotes with emphasis on studies involving
Escherichia coli and Saccharomyces cerevisiae . While the
molecular mechanisms of degradation in bacteria and
yeast appear somewhat different, we argue that the under-
lying causes of ribosome degradation are remarkably sim-
ilar. In both model organisms during ribosomal assembly,
partially formed pre-ribosomal particles can be degraded
by at least two different sequentially-acting quality con-
trol pathways and fully assembled but functionally faulty
ribosomes can be degraded in a separate quality control
pathway. In addition, ribosomes that are both structur-
ally- and functionally-sound can be degraded as an adap-
tive measure to stress.
Keywords: degradation; Escherichia coli ; nonfunctional
RNA decay (NRD); ribosome; yeast.
*Corresponding author: Ü lo Maiv ä li, Institute of Technology,
University of Tartu, Nooruse 1, Tartu 50411, Estonia,
e-mail: [email protected]
Anton Paier and Tanel Tenson: Institute of Technology, University of
Tartu, Nooruse 1, Tartu 50411, Estonia
Introduction Traditionally, cellular RNAs have been described as either
unstable or stable. Messenger RNAs (mRNAs) are typical
of unstable RNAs, with lifetimes from minutes to hours,
while ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs)
are often viewed as stable, with lifetimes that can exceed
several weeks (Metodiev et al. , 2009 ). This dichotomy
of stability regimes is intuitively well supported by the
notion that it must be advantageous to maintain a rapid
turnover of mRNA to enable rapid suppression of the syn-
thesis of individual proteins by stopping transcription of
their genes. In contrast, RNAs that perform housekeeping
functions should ideally live forever to reduce the cost of
making them. The cost of making ribosomes is consider-
able. In exponentially-growing bacterial cells, about 80%
of transcriptional activity can be accounted for by pre-
rRNA synthesis (most of the remainder being tRNA syn-
thesis) and up to 25% of protein synthesis activity is dedi-
cated to making r-proteins (Bremer and Dennis , 1987 ). The
situation appears similar in growing yeast, where 60% of
total transcription is of rRNA and, in addition, 50% of the
newly-made mRNAs code for ribosomal proteins (Warner ,
1999 ). Compared to the expenditures for rRNA synthe-
sis, the cost of making mRNAs is negligible. Indeed, the
number of active ribosomes is growth-limiting for a wide
variety of single-celled organisms, bacterial and other
(Scott et al. , 2010 ; Ehrenberg et al. , 2013 ). This suggests
that ribosome production could be maximized for speed
and that ribosomal degradation could directly slow cell
growth.
There are, however, three reasons why degrading ribo-
somes might be a good idea at least some of the time. First,
the assembly process is complex with numerous possibili-
ties for introducing errors. Each Escherichia coli ribosome
consists of two large rRNAs, one medium-size rRNA and
about 54 carefully assembled r-proteins; eukaryotic ribo-
somes being more complex still. Considering that the syn-
thesis of individual ribosomal components is unlikely to
be completely stoichiometric and their assembly involves
inefficiencies, timely degradation of ribosomal precursors
stuck on some unproductive sidetrack of their assembly
landscape is likely to be beneficial. Second, because ribo-
somes are normally long-lived, random chemical damage
may accumulate and lead to a gradual loss of function.
These errors can either be rectified by ribosomal repair or
degradation. Third, while a large number of ribosomes are
required for rapid cellular growth, during stress and star-
vation they may be viewed as readily usable repositories
of building blocks for new proteins and nucleic acids; one
cannot grow tomorrow if dead today.
In this review we will sift through current literature rel-
evant for these three scenarios of ribosome degradation,
including references to eukaryotic systems. In addition to
the why of ribosome degradation, molecular mechanisms
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846 Ü . Maiv ä li et al.: Ribosome degradation
of degradation will not be neglected. Emphasis is given to
recent research as there are excellent reviews of the clas-
sics (Deutscher , 2003, 2006, 2009 ).
Degradation of misassembled pre-ribosomes Assembly of ribosomal subunits begins co-transcription-
ally. In E. coli the ribosomal RNAs are synthesized from
5500 nt operons, of which there are seven copies (there
is an extra, eighth, copy of the 5S rRNA gene). As a first
step, this long transcript is cleaved to pre-16S rRNA, and
pre-23S rRNA molecules by the double-stranded RNA-spe-
cific endonuclease ribonuclease III (RNase III) and these
are consequently trimmed to full-length rRNAs by RNase
E, RNase G, RNase T, RNase PH and YbeY (Kaczanowska
and Ryden -Aulin, 2007 ; Deutscher , 2009 ; Davies et al. ,
2010 ; Shajani et al. , 2011 ; Gutgsell and Jain , 2012 ). Analo-
gously, pre-5S rRNA is created by a digestion at each end
by RNase E. The binding of r-proteins to precursor rRNA is
already required for correct cleavage of pre-23S rRNA by
RNase III (Allas et al. , 2003 ). During the assembly process,
three ribosomal RNAs meet about 54 r-proteins, the rRNAs
undergo at least 38 separate post-transcriptional modifi-
cations and 11 r-proteins accrue one or more modifications
of their own (Kaczanowska and Ryden -Aulin, 2007 ). The
compositions of exponential growth phase and stationary
phase ribosomes are slightly different: stationary phase
ribosomes contain an extra r-protein (S22), a different
isoform of the L31 protein, and increased amounts of the
acetylated L7 as part of the L7/L12 complex (Ramagopal
and Subramanian , 1974 ; Wada , 1998 ; Nanamiya et al. ,
2004 ). The functional consequences of these differences
remain largely unexplored.
Ribosomal assembly can be mimicked in vitro by
mixing rRNAs with purified r-proteins and incubating the
mixture over extended periods of time under different
non-physiological temperatures (Nierhaus and Dohme ,
1974 ). In living cells the process is relatively fast and
catalyzed by over 20 extra-ribosomal proteins, includ-
ing RNA helicases, ribosome-dependent GTPases, RNA,
and protein chaperones (Kaczanowska and Ryden -Aulin,
2007 ; Shajani et al. , 2011 ). Although the assembly process
is not understood in detail, it is likely that it occurs via
multiple parallel pathways each of which contain rate-
limiting intermediates and unproductive side-paths
(Shajani et al. , 2011 ). A main function of the extra-riboso-
mal assembly factors is to rescue partly assembled parti-
cles from the kinetic traps and cul-de-sac ’ s of the assembly
landscape, thus providing them with new opportunities
to find paths that lead to functional ribosomes. Other
possible functions for assembly factors include blocking
of premature translation by competition for the binding
sites of substrates for translation initiation, blocking
the premature formation of native structural elements
and premature binding of specific r-proteins, as well as
the stabilization and destabilization of pre-ribosomes
(Shajani et al. , 2011 ; Karbstein , 2013 ). In a classic work,
Gausing compared the relative synthesis and accumu-
lation rates of rRNA at different growth rates, which
enabled her to estimate both assembly efficiencies and
rRNA degradation (Gausing , 1977 ). Degradation appears
negligible during rapid growth, while during very slow
growth only about one-third to half of the newly-made
rRNA is incorporated into stable ribosomes. Using similar
methods, upon nutritional down-shift it was shown that
about 50% fewer ribosomes accumulated as mature
particles than were made as rRNAs (Molin et al. , 1977 ).
These results imply widespread co-assembly ribosomal
precursor degradation in E. coli . Accordingly, RNA puri-
fied from fast-growing E. coli degradosomes consisted
predominantly of rRNA fragments while lacking tRNA
(Bessarab et al. , 1998 ). The degradosome, which consists
of the endonuclease RNase E, the 3 ′ – 5 ′ exonuclease poly-
nucleotide phosphorylase (PNPase), the DEAD-box RNA
helicase RhlB, and the glycolytic enzyme enolase, was
recently shown to interact with mature ribosomes (Tsai
et al. , 2012 ). In addition to PNPase, which is implicated in
ribosome degradation (Basturea et al. , 2011 ), RNase E is
involved in pre-rRNA processing, and is the major RNAse
in mRNA degradation. Elucidation of the functional role
of degradosome-ribosome interaction awaits further
study. It stands to reason that the RNase E endonuclease,
which is readily inhibited by the multitude of structured
elements in correctly-folded rRNA, could nevertheless
recognize and cut misfolded rRNAs that are expected to
have more single-stranded regions. Degradation of mis-
assembled rRNA is likely to be initiated by an endonucle-
ase and to require polyadenylation of degradation inter-
mediates (Maes et al. , 2011 ), which are in turn substrates
for PNPase and RNase R (Basturea et al. , 2011 ). Polyade-
nylation also plays a pivotal role in the degradation of
misassembled tRNA molecules with the participation of
PNPase (Li et al. , 2002 ).
In eukaryotes, rRNAs are synthesized from operons
as in bacteria, but they are longer, are processed in more
complex pathways, are more heavily modified and associ-
ate with about 80 different r-proteins. Accordingly, in yeast
there are around 200 extra-ribosomal assembly factors to
expedite the process (Henras et al. , 2008 ). It seems that as
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Ü . Maiv ä li et al.: Ribosome degradation 847
QC 2
Nob1p
QC 3Exosome
ProteasomeRepair?
RNase T2
Exosome
QC 1
Nucleolus
No-body
16S 23S 5S
Assemblyintermediates
QC 1Exosome, PAP
QC 2YbeY, RNase R
Matureribosomes
YbeY
QC 3
Repair?
100S70S-YbiA70S-YgjD
RNases II, PH, R
Transcription of rrn operon
P body
Ribophagy110S
Recycling
Assembledparticles
Active ribosomes
Recycling
Stress Stress
18S 5,8S 28S
30S 50S 40S60S
60S
40S
ExosomeTRAMP
Ribosomedegradation
Bacteria Yeast
Figure 1 A comparative scheme of Escherichia coli (left) and yeast (right) ribosomal metabolism.
QC 1: The first quality control pathway that degrades ribosomal assembly intermediates using exosome, bacterial poly(A) polymerase (PAP)
and the yeast nuclear poly(A) polymerase complex (TRAMP). QC 2: The second quality control pathway that uses the last processing step of
the 3 ′ -end of the small subunit RNA as a mark for successful assembly of the small subunit. QC 2 requires association of the small subunit
with the large ribosomal subunit to function. QC 3: The third quality control pathway, Non-functional Ribosome Decay (NRD) removes
structurally-sound but functionally-deficient mature ribosomes. In yeast, the inactive 40S and 60S subunits are degraded independently by
different mechanisms. 40S NRD is localized in P bodies and uses the cytoplasmic exosome. The 60S NRD is initiated by r-protein degrada-
tion and occurs in the cytoplasm. The existence of bacterial QC 3 is unclear. Recycling: degradation of ribosomes in response to stress
(including starvation). 100S, 110S, 70S – YbiA and 70S – YgjD denote different inactive ribosomal complexes that are used for ribosome
storage during the stationary growth phase.
the number of components that have to be co-assembled
increases from bacteria to yeast by about 1.5-fold the com-
plexity of the task, as measured by the number of aux-
iliary factors needed for speedy assembly, increases by
about 10-fold. The assembly process starts co-transcrip-
tionally in the nucleolus, where assembly intermediates
can be degraded by the nuclear exosome and continues
after transport at the rate of 2000 ribosomes per minute
to the cytoplasm (Warner , 1999 ; Allmang et al. , 2000 ).
Pre-ribosomes that are in principle able to participate in
(and potentially to interfere with) protein synthesis are
transported to the cytoplasm in an inactivated form with
several trans-factors bound to active sites, thus preclud-
ing initiation of translation (Panse and Johnson , 2010 ).
After successful transport of pre-ribosomes to the cyto-
plasm there is a final quality control checkpoint of 40S
subunits (Figure 1 ). It seems that 40S subunits that still
contain pre-18S rRNAs lacking the final 3 ′ -end processing
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848 Ü . Maiv ä li et al.: Ribosome degradation
are assembled into translationally inactive 80S ribosomes
solely for quality control purposes (Lebaron et al. , 2012 ;
Strunk et al. , 2012 ). Kinetic competition between the final
processing of pre-18S rRNA by the Nob1p endonuclease
and degradation of the ribosome by unknown means will
ensue (Strunk et al. , 2012 ). In order for the final matura-
tion of the 18S rRNA to occur, the pre-40S must be able
to correctly bind the 60S and participate in the activation
of its GTPase center. The mature 3 ′ -end of the 18S rRNA
would thus serve as a mark that signifies the structural
soundness of the 40S particle. A strikingly similar quality
control mechanism was recently described in E. coli (Jacob
et al. , 2013 ). In this mechanism, the final processing of the
3 ′ -end of pre-16S rRNA is dependent on 70S ribosome for-
mation. Both the ensuing processing step and the alter-
native (ribosome degradation) involve the YbeY protein,
thus making it a prime suspect for the endonuclease that
triggers ribosomal degradation in E. coli . Interestingly,
ribosomes were not only degraded in the absence of
pre-16S rRNA 3 ′ -end processing, but also when ribosomal
structure was perturbed in the presence of the antibiotic
kasugamycin (Jacob et al. , 2013 ). This rhymes with studies
showing that several other ribosome-binding antibiot-
ics can lead to both defective ribosomes and destabiliza-
tion of rRNA (Silvers and Champney , 2005 ; Frazier and
Champney , 2012 ) and suggests a general role for the
YbeY quality control pathway in dealing with structurally
unsound ribosomes.
As in bacteria, misassembled eukaryotic ribosomes
are expected to be scavenged for parts. Interestingly,
all 11 3 ′ – 5 ′ exonucleases of the yeast nuclear exosome
were genetically linked to multiple indirect roles in
various early endonucleolytic pre-rRNA processing steps
(Allmang et al. , 2000 ). As all direct action in these pro-
cessing steps is taken by endonucleases, the most likely
role for the exosome was thought to be in degrading mis-
assembled ribosomal precursor particles (Allmang et al. ,
2000 ). Nuclear pre-ribosomes destined for degradation
are localized to a specific sub-nucleolar compartment
(the No-body), are polyadenylated by the TRAMP complex
and degraded on the spot by the exosome (Dez et al. ,
2006 ). Similar TRAMP-exosome pathway of rRNA degra-
dation seems to be active in the cytoplasm of human cells
(Slomovic et al. , 2010 ). Six of the yeast exosome com-
ponents are homologous to E. coli RNase PH and one to
RNase R, both of which, together with the degradosome
component PNPase, are implicated in bacterial ribosome
degradation (Zhou and Deutscher , 1997 ; Deutscher , 2009 ;
Basturea et al. , 2011 ; Frazier and Champney , 2012 ). The
importance of co-assembly quality control is emphasized
by work indicating that failures thereof are associated
with multiple human diseases (Freed et al. , 2010 ; Narla
and Ebert , 2010 ).
Degradation of inactive ribosomes From the motley crew of ribosomal precursor particles
that pass muster at the quality control steps beautiful
ribosomes are born. Some, however, are still poor at their
primary job of making new proteins. Co-assembly quality
control is likely to recognize larger structural defects,
however it is probable that ribosomes with smaller but
still inactivating changes (mutations or chemical damage)
also occur and duly make trouble when entering poly-
somes. Chemical damage to rRNA and ribosome dysfunc-
tion has been associated with the early stages of human
neurodegenerative disease (Ding et al. , 2005 ; Nunomura
et al. , 2012 ) and with accelerated ribosomal degrada-
tion in yeast (Mroczek and Kufel , 2008 ). Likely actions
against damaged ribosomes include repair and degrada-
tion. Stable cellular RNAs are readily oxidized by H 2 O
2
treatment in E. coli (Liu et al. , 2012 ) and PNPase has been
implicated in coping with chemically-damaged RNA from
E. coli to human cells (Wu and Li , 2008 ; Wu et al. , 2009 ).
While functional repair of chemically-damaged
mRNA and tRNA by the AlkB demethylase has been
described (Ougland et al. , 2004 ), possible repair of rRNA
has so far escaped scrutiny. There is, however, evidence
for the rejuvenation of E. coli ribosomes by exchanging
r-proteins from elderly ribosomes for newly-made pro-
teins (Pulk et al. , 2010 ). About 10 different r-proteins
were exchangeable in vivo when measured over 3 h in
stationary-phase cultures while in vitro experiments
suggest that several more could be efficiently exchanged
in principle (Pulk et al. , 2010 ). The physiological impor-
tance of r-protein exchange is as yet unknown.
Degradation of functionally-inactive but fully-assem-
bled ribosomal subunits was first discovered in yeast,
where inactivating point mutations in the decoding center
of the 18S rRNA led to degradation of the 40S ribosomal
subunit, and mutations in the 28S rRNA peptidyl trans-
ferase active site led to degradation of the 60S subunit
(LaRiviere et al. , 2006 ). Quality control mechanisms rec-
ognize the damage at the level of 80S ribosomes. Inter-
estingly, only the mutationally inactivated subunits were
degraded while their wild-type binding partners were
stable, leading to a relative depletion of mutant rRNA
(LaRiviere et al. , 2006 ). Mutations at equivalent positions
of E. coli rRNAs do not lead to similar depletion. This fact
prompted a suggestion that E. coli does not degrade its
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Ü . Maiv ä li et al.: Ribosome degradation 849
inactive but its fully-assembled ribosomes (LaRiviere
et al. , 2006 ). However, as is common in biology, the
truth may turn out to be more complex. A recent paper
suggests that the YbeY endonuclease requires structur-
ally-defective 30S subunits that are assembled into 70S
ribosomes to initiate ribosomal degradation (Jacob et al. ,
2013 ). This not only identifies YbeY as a potential initi-
ating endonuclease for ribosome degradation but also
raises a strong possibility of a nonfunctional RNA decay
(NRD)-like process in E. coli . Strikingly, both the defective
30S subunit and the associated healthy 50S subunit were
degraded (Jacob et al. , 2013 ).
A different conclusion was reached by Zundel et al.
(2009) , who showed that subjecting dissociated riboso-
mal subunits, but not 70S ribosomes, to cellular extracts
led to moderate degradation of both 16S rRNA and 23S
rRNA over 45-min incubation at 37 ° C (Zundel et al. , 2009 ).
To clarify the presence or absence of nonfunctional rRNA
decay in E. coli , additional experimental effort is required.
The mechanisms of NRD are being increasingly
exposed in the yeast system and appear to be rather
exciting. The first surprise is that small and large sub-
units are degraded by very different mechanisms. Degra-
dation of the defective and consequently translationally-
stalled small 40S subunits utilizes the same cytoplasmic
No-Go Decay (NGD) pathway as degradation of the mRNA
caught in the stalled ribosome (Cole et al. , 2009 ). The
stalled 80S ribosome is attacked by the NGD effector pro-
teins Hbs1p, Ski7p, Hbs1p, and Dom34p and the major
cytoplasmic 5 ′ – 3 ′ exonuclease Xrn1p. It is likely that the
Dom34p:Hbs1p complex dissociates the 60S subunit
from the stalled translational complex (Tsuboi et al. ,
2012 ). Subsequently, 18S rRNA is degraded by the cyto-
plasmic exosome localized in P bodies, along with the
mRNA that is degraded by the same pathway (Cole et al. ,
2009 ; Lafontaine , 2010 ).
The second surprise is that inactive large subunits
(60S) are degraded not only by a different mechanism but
that degradation starts from proteins, not rRNA. Initially
the E3 ubiquitin ligase complex ubiquitylates several pro-
teins (Fujii et al. , 2009 ). The defective 60S subunits are
then dissociated from the 80S ribosomes with the help of
Cdc48 ubiquitin binding complex and 60S degradation is
initiated by the proteasome (Fujii et al. , 2012 ). Only then
does the 28S rRNA degradation commence, possibly cata-
lyzed by the cytoplasmic exosome near the nuclear enve-
lope (and thus not localized to the P bodies) (Cole et al. ,
2009 ). The 40S subunit that was bound to the mutant 60S
subunit is likely to dissociate from mRNA and to be reuti-
lized in a next round of initiation, therefore avoiding the
need to degrade it via the NGD pathway.
Ribosomal degradation in stress There is a downside to the ubiquity of ribosomes. During
many growth conditions ribosome concentrations limit
the growth rates (Scott et al. , 2010 ) and, therefore, the
more the merrier. However, cessation of growth can mean
trouble. The once rate-limiting protein synthesis now
turns into a more specialized affair, making most ribo-
somes a surplus product of the cellular economy. As with
any surplus, ribosomes can either be stored in anticipa-
tion of better days or recycled. Indeed, there is convincing
evidence that upon entry to the stationary phase many
ribosomes are stored as inactivated 100S dimers, 70S mon-
omers or dissociated subunits, and this process is rapidly
reversible when growth resumes (Agafonov et al. , 1999 ;
El -Sharoud, 2004 ). Testing several natural E. coli isolates
in batch culture revealed that over half of the ribosomes
are present as 100S at the onset of the stationary phase
(Wada et al. , 2000 ). Upon continuance of the stationary
phase, these ribosomal dimers mostly dissociated after a
few hours, only to re-engage for several more days. This
was followed by the final dissolution and degradation of
ribosomes concomitant with loss of viability (Wada et al. ,
2000 ). Two proteins, RMF and HPF, are required for 100S
formation. RMF binds to the 30S subunit and blocks anti-
Shine-Dalgarno:Shine-Dalgarno (anti-SD:SD) interaction
between 16S rRNA and mRNA. HPF blocks the tRNA, IF1
and IF3 binding sites (Polikanov et al. , 2012 ).
A second alternative for ribosome storage is by inac-
tivation of the ribosome in the 70S or at the subunit
level. There seem to be several ways to achieve this. For
example, binding of the YfiA protein, which has a par-
tially overlapping binding site with HPF, leads to inac-
tive 70S formation (Polikanov et al. , 2012 ). A family of
proteins, exemplified by YqjD, inactivate the station-
ary phase ribosomes and tie them to cell membranes in
E. coli (Yoshida et al. , 2012 ). A third alternative is that
RsfA (also known as YbeB) protein inactivates stationary-
phase ribosomes by binding to the 50S and dissociating
the subunits ( H ä user et al. 2012 ). Recently, stress-induced
reversible ribosomal 110S dimers were found in rat (but
not in mouse or human) cell lines, hinting that multicel-
lular organisms might use similar strategies of ribosomal
storage upon cessation of growth (Krokowski et al. , 2011 ).
While bacterial ribosome dimers are connected by the
small subunits, the mammalian version appeared to be
connected by the 60S large subunits.
In an instance of ribosome reorganization, during
various stress conditions including stringent response,
oxidative stress and heat shock, 43 nucleotides can
be cleaved from the 3 ′ -end of the mature 16S rRNA by
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850 Ü . Maiv ä li et al.: Ribosome degradation
the endonuclease MazF (Vesper et al. , 2011 ; Moll and
Engelberg -Kulka, 2012 ). This is likely to happen in fully
assembled ribosomes and results in the accumulation
of specific stress ribosomes that lack anti-SD sequences.
Stress ribosomes reprogram global translation pat-
terns giving preference to leaderless mRNAs lacking SD
sequences (Vesper et al. , 2011 ). Interestingly, the same
MazF endonuclease also cleaves several mRNAs, con-
verting them into a conveniently leaderless form for the
benefit of the stress ribosomes (Vesper et al. , 2011 ).
So far we have looked at ribosome degradation caused
either by defective processing and/or assembly of the pre-
ribosomes or by the defective structure of the mature ribo-
somes. In fact, most studies on ribosomal degradation
over the past 50 years have focused on the degradation
of functionally-healthy ribosomes. This work has focused
on various cellular stress conditions in E. coli , starting
with Mg 2 + starvation (Aronson and McCarthy , 1961 ) and
including starvation of phosphate, nitrogen, and carbon,
growth in a minimal sea-salt medium, overexpression
of an ectopic protein containing many rare codons, and
increased membrane permeability (Kaplan and Apirion ,
1975 ; Davis et al. , 1986 ; Dong et al. , 1995 ; Kalpaxis et al. ,
1998 ; Deutscher , 2003, 2006, 2009 ). These experiments
all have at least one thing in common: degradation is
mea sured in non-growing stressed cells. In physically-
damaged dying bacterial cells, RNase I can move from its
normal periplasmatic location to the cytoplasm and effi-
ciently degrade ribosomes (Deutscher , 2009 ). In plants,
the RNase I homologue, RNase T2, is located in the endo-
plasmic reticulum and vacuoles, and is thought to be
involved in ribosome recycling under normal conditions
(Hillwig et al. , 2011 ), as are several RNase T2 enzymes of
the ciliate Tetrahymena (Andersen and Collins , 2011 ) and
lysosomal RNase T2 enzymes of fish and humans (Mac-
Intosh , 2011 ). In plants and fungi the RNase T2 enzymes
have been proposed to participate in starvation-induced
phosphate recycling from the ribosomes (MacIntosh ,
2011 ). In E. coli there seems to be an active mechanism
by which the ribosomes inhibit RNase I and thus protect
themselves (Kitahara and Miyazaki , 2011 ). Protection
from degradation is provided by sequestering of RNase I
to helix 41 of the 16S rRNA. This protection of ribosomes
from RNase I increased viability in stationary phase and
greatly increased survival upon artificial depolarization
of the inner cell membrane (Kitahara and Miyazaki , 2011 ).
During starvation in E. coli , the cytoplasmic exonucle-
ases RNase PH, RNase II and RNase R are important for
the removal of rRNA fragments while the endonuclease(s)
that initiate rRNA degradation, apart from RNase I, remain
unknown (Deutscher , 2009 ; Basturea et al. , 2011 ).
While the above implies that ribosomal degradation
can kill, interesting data presented by Basturea et al.
suggest that in some cases degrading most of your ribo-
somes can be life-saving (Basturea et al. , 2012 ). They
showed that switching E. coli cultures from phosphate to
arsenate led to degradation of the ribosomes. After the
switch, culture growth stopped for about 80 h after which
a small tolerant cell population resumed growth. The sim-
plest explanation is that such growth must use phosphate
released from degraded ribosomes as the major source of
this essential element. This kind of reasoning is echoed in
yeast, where many cellular recycling pathways, including
ribosome breakdown, were proposed to be required for
stress survival (Davey et al. , 2012 ).
Nevertheless, to degrade functional ribosomes the
cells do not have to be facing death. Even growing E. coli batch cultures can exhibit widespread ribosome degrada-
tion that coincides with a slowing of culture growth before
the onset of the stationary phase (Piir et al. , 2011 ). This
degradation of ribosomal RNA is genetically independ-
ent of the stringent response, which is the major cellular
pathway for coping with nutrient starvation by inhibi-
ting ribosome synthesis and generally reorganizing gene
expression (Dalebroux and Swanson , 2012 ). Interestingly,
ribosomes were stable during both constant rate growth
and in the actual stationary phase (Piir et al. , 2011 ). A
similar degradation pattern of ribosomes during prepara-
tion for stationary phase entry was previously described
in various Salmonella strains, where rRNA is normally
fragmented by specific RNase III cleavages and yet consti-
tutes fully functional ribosomes (Hsu et al. , 1994 ). Riboso-
mal degradation that precedes the stationary phase could
either represent an active coping strategy or be an unfor-
tunate cause for the cessation of growth. In this respect,
the emerging picture of the regulation of a major rRNA
degrading enzyme, RNase R, is of note (Figure 2 ). The
E. coli RNase R protein is normally extremely unstable
with a half-life of about 10 min (Chen and Deutscher ,
2010 ). During cold shock, growth on minimal medium
and entry into stationary phase the protein is stabi-
lized so that, even while its mRNA levels are reduced,
its level increases by several-fold (Chen and Deutscher ,
2005 , 2010). In exponentially growing cells, the RNase R
protein is acetylated at a single Lys-residue by the lysyl
acetyltransferase (Pka), which in turn is absent from
late-exponential phase and stationary phase cells (Liang
and Deutscher , 2011 ). The presence of the acetylation is
required for the binding of the tmRNA-SmpB complex to
RNase R (Liang and Deutscher , 2012a ), which in turn leads
to degradation of RNase R by the HslUV and Lon proteases
(Liang and Deutscher , 2012b ). As the well-established
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Ü . Maiv ä li et al.: Ribosome degradation 851
function of the tmRNA-SmpB complex is to rescue stalled
ribosome-mRNA complexes, it stands to reason that under
conditions where more ribosome stalling occurs less
tmRNA-SmpB will be available to destabilize RNase R and
this could lead to increased ribosome degradation. While
RNase R is stabilized in the stationary phase, the Lon pro-
tease is activated by the accumulation of polyphosphate
concomitant with stationary phase onset (Ault -Rich é
et al., 1998 ; Kuroda et al. , 2001 ). The Lon-catalyzed pro-
teolysis upon nutritional downshift leads to degrada-
tion of about 15% of cellular protein, including partial
degradation of most ribosomal proteins (Kuroda et al. ,
2001 ). This proteolysis activity generates a fresh pool of
reusable amino acids and is necessary for E. coli growth
during nutritional downshifts (Kuroda et al. , 1999, 2001 ).
Polyphosphate synthesis is stimulated by ppGpp, suggest-
ing a role for stringent response in the degradation of ribo-
somal proteins (Kuroda et al. , 1997 ), if not for ribosomal
RNA (Piir et al. , 2011 ).
Similarly, upon ribosome degradation in yeast, most
r-proteins are degraded rapidly while the ones that have
extraribosomal functions or are otherwise required in a
free cytoplasmatic pool may use specific mechanisms of
stabilization (Nusspaumer et al. , 2000 ; Jia et al. , 2012 ).
It is interesting to compare these bacterial processes
with active ribosome degradation in eukaryotes. In yeast
growing rapidly in a nutrient rich medium, cytoplasmic
ribosomes are protected from degradation by the ubiquitin
ligase Rsp5 (Shcherbik and Pestov , 2011 ). When nutrients
become limiting, ribosomal degradation commences in
yeast cultures that continue to grow (Johnston et al. , 1977 ;
Ju and Warner , 1994 ). The magnitude of degradation
appears to be controlled by the ribosome-associated
protein Stm1p to allow for enough remaining translational
capacity for optimal outgrowth upon nutrient upshift
(Van Dyke et al. , 2013 ). During nitrogen starvation, despite
the fact that both RNA and protein synthesis continue, no
net accumulation of RNA due to concomitant RNA deg-
radation occurs (Johnston et al. , 1977 ). Thus a surprising
picture emerges: during nutrient limitation the synthesis
of ribosomes is accompanied by concomitant degrada-
tion. This seems to hold true for both bacteria and yeast.
In yeast, mature ribosomes are degraded on nutrient
limitation by a selective type of autophagy (ribophagy),
which requires the Ubp3/Bre5 ubiquitin protease (Kraft
et al. , 2008 ; Cebollero et al. , 2012 ). This pathway is not
inhibited by the Rsp5 ubiquitin ligase (Shcherbik and
Pestov , 2011 ). Ubp3 Δ cells are not only sensitized to nutri-
ent limitation but also to rapamycin, a drug that inhibits
the central target of rapamycin (TOR) signaling pathway
(Kraft et al. , 2008 ). Inhibition of the TOR pathway leads to
growth inhibition through the global inhibition of protein
synthesis, inhibition of the synthesis of new ribosomes,
as well as leading to a large-scale degradation of cytoplas-
mic ribosomes (Pestov and Shcherbik , 2012 ). Although
rapamycin-induced degradation requires the cytoplasmic
exosome for scavenging of rRNA degradation intermedi-
ates, it appears to be genetically distinct from non-func-
tional ribosome decay and from the ribophagy pathway
(Pestov and Shcherbik , 2012 ). It is therefore likely that
this type of ribosome degradation utilizes a yet another
uncharacterized molecular pathway.
Pka
Starvation: slowing growthExponential growth
Ac
E P A 50S
30S
Polyphosphate
AcAc
rRNA fragments
Lon
r-proteinsrRNA deg
RNase Rdeg
r-proteins
SmpB-tmRNA
Rnase R
Figure 2 Regulation of starvation-induced ribosomal degradation in Escherichia coli . During fast growth, RNase R is acetylated by Pka, the acetylated form binds SmpB-tmRNA, which in turn recruits the Lon protease to
degrade RNase R. Starvation represses Pka expression leaving stabilized RNase R free to degrade ribosomes. During starvation, SmpB-
tmRNA binds to stalled ribosomes, terminates the nascent peptide and helps to dissociate the ribosomal subunits. Dissociated subunits
are susceptible to degradation. While ensuing rRNA fragments are scavenged by RNase R and RNase PH, many basic r-proteins are likely to
bind to highly-charged polyphosphate, which is synthesized in the stationary growth phase, and is subsequently degraded by Lon, which
also binds to polyphosphates.
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852 Ü . Maiv ä li et al.: Ribosome degradation
In addition to the control of cellular proliferation,
ribosome degradation is associated with apoptosis from
yeast to humans (King et al. , 2000 ; Hoat et al. , 2006 ;
Mroczek and Kufel , 2008 ), diabetes in rats (Ashford and
Pain , 1986 ) and the colony collapse disorder in honey
bees (Johnson et al. , 2009 ).
Future directions The relative plentitude of situations where ribosomes are
degraded in conjunction with the number of different
degradation pathways that seem to be required lead to the
happy conclusion that there are things yet to look forward
to in the ribosome degradation field. We still know very
little about the mechanisms that trigger the various ribo-
somal quality control pathways. A glaring omission, that
has just begun to be looked into, is the identities and
modes of action of the endonucleases that initiate ribo-
somal degradation. The presence and possible nature of
a NRD-like pathway in bacteria clearly warrants further
study. We believe that as ribosomal degradation is but
one solution to various problems arising in the cellular
economy, this process cannot be fully understood without
sufficient understanding of the catalysis of ribosome
assembly, repair and storage.
Now that instances of degradation of the most ubiqui-
tous stable RNAs, including tRNAs, are revealed in increas-
ing numbers (Thompson and Parker , 2009 ; Wilusz et al. ,
2011 ; Dewe et al. , 2012 ), a rather obvious question arises:
how stable are the other stable ribonucleoproteins ? These
include the RNase P ribonucleoprotein, the various splice-
osomes, and small nucleolar ribonucleoproteins involved
in RNA modification, and others, all of which could benefit
from quality control and regulation at the level of degrada-
tion. Lessons learned in the ribosome could thus help to shed
new light to superficially-unrelated biological questions.
Acknowledgements: We thank Aivar Liiv and David
Schryer for helpful comments on the manuscript and Sille
Hausenberg for help with preparing the figures. This work
was supported by the Estonian Science Agency grant no
9040 and by the European Regional Development Fund
through the Center of Excellence in Chemical Biology.
Received February 7, 2013; accepted March 20, 2013; previously
published online March 24, 2013
References Agafonov, D.E., Kolb, V.A., Nazimov, I.V., and Spirin, A.S. (1999).
A protein residing at the subunit interface of the bacterial
ribosome. Proc. Natl. Acad. Sci. USA 96 , 12345 – 12349.
Allas, U., Liiv, A., and Remme, J. (2003). Functional interaction
between RNase III and the Escherichia coli ribosome. BMC Mol.
Biol. 4 , 8.
Allmang, C., Mitchell, P., Petfalski, E., and Tollervey, D. (2000).
Degradation of ribosomal RNA precursors by the exosome.
Nucleic Acids Res. 28 , 1684 – 1691.
Andersen, K.L., and Collins, K. (2011). Several RNase T2 enzymes
function in induced tRNA and rRNA turnover in the ciliate
Tetrahymena. Mol. Biol. Cell 23 , 36 – 44.
Aronson, A.I. and McCarthy, B.J. (1961). Studies of E. coli ribosomal RNA and its degradation products. Biophys. J. 1 ,
215 – 226.
Ashford, A.J. and Pain, V.M. (1986). Effect of diabetes on the rates of
synthesis and degradation of ribosomes in rat muscle and liver
in vivo. J. Biol. Chem. 261 , 4059 – 4065.
Ault-Rich é , D., Fraley, C.D., Tzeng, C.M., and Kornberg, A. (1998).
Novel assay reveals multiple pathways regulating stress-
induced accumulations of inorganic polyphosphate in
Escherichia coli. J. Bacteriol. 180 , 1841 – 1847.
Basturea, G.N., Zundel, M.A., and Deutscher, M.P. (2011).
Degradation of ribosomal RNA during starvation: comparison
to quality control during steady-state growth and a role for
RNase PH. RNA 17 , 338 – 345.
Basturea, G.N., Harris, T.K., and Deutscher, M.P. (2012). Growth of a
bacterium that apparently uses arsenic instead of phosphorus
is a consequence of massive ribosome breakdown. J. Biol.
Chem. 287 , 28816 – 28819.
Bessarab, D.A., Kaberdin, V.R., Wei, C.L., Liou, G.G., and Lin-Chao, S.
(1998). RNA components of Escherichia coli degradosome:
evidence for rRNA decay. Proc. Natl. Acad. Sci. USA 95 ,
3157 – 3161.
Bremer, H. and Dennis, P.P. (1987). Modulation of chemical
composition and other parameters of the cell by growth rate.
In: Escherichia coli and Salmonella typhimurium: Cellular
and Molecular Biology. (American Society for Microbiology,
Washington, DC), pp. 1527 – 1542.
Cebollero, E., Reggiori, F., and Kraft, C. (2012). Reticulophagy
and ribophagy: regulated degradation of protein production
factories. Int. J. Cell Biol. 2012 , 182834.
Chen, C. and Deutscher, M.P. (2005). Elevation of RNase R in
response to multiple stress conditions. J. Biol. Chem. 280 ,
34393 – 34396.
Chen, C. and Deutscher, M.P. (2010). RNase R is a highly unstable
protein regulated by growth phase and stress. RNA 16 ,
667 – 672.
Cole, S.E., LaRiviere, F.J., Merrikh, C.N., and Moore, M.J. (2009).
A convergence of rRNA and mRNA quality control pathways
revealed by mechanistic analysis of nonfunctional rRNA decay.
Mol. Cell 34 , 440 – 450.
Brought to you by | Tartu University LibraryAuthenticated
Download Date | 1/29/15 12:45 PM
Ü . Maiv ä li et al.: Ribosome degradation 853
Dalebroux, Z.D. and Swanson, M.S. (2012). ppGpp: magic beyond
RNA polymerase. Nat. Rev. Microbiol. 10 , 203 – 212.
Davey, H.M., Cross, E.J.M., Davey, C.L., Gkargkas, K., Delneri, D.,
Hoyle, D.C., Oliver, S.G., Kell, D.B., and Griffith, G.W. (2012).
Genome-wide analysis of longevity in nutrient-deprived
Saccharomyces cerevisiae reveals importance of recycling
in maintaining cell viability. Environ. Microbiol. 14 ,
1249 – 1260.
Davies, B.W., K ö hrer, C., Jacob, A.I., Simmons, L.A., Zhu, J.,
Aleman, L.M., RajBhandary, U.L., and Walker, G.C. (2010).
Role of Escherichia coli YbeY, a highly conserved protein, in
rRNA processing. Mol. Microbiol. 78 , 506 – 518.
Davis, B.D., Luger, S.M., and Tai, P.C. (1986). Role of ribosome
degradation in the death of starved Escherichia coli cells.
J. Bacteriol. 166 , 439 – 445.
Deutscher, M.P. (2003). Degradation of stable RNA in bacteria.
J. Biol. Chem. 278 , 45041 – 45044.
Deutscher, M.P. (2006). Degradation of RNA in bacteria: comparison
of mRNA and stable RNA. Nucleic Acids Res. 34 , 659 – 666.
Deutscher, M.P. (2009). Maturation and degradation of ribosomal
RNA in bacteria. Prog. Mol. Biol. Transl. Sci. 85 , 369 – 391.
Dewe, J.M., Whipple, J.M., Chernyakov, I., Jaramillo, L.N., and
Phizicky, E.M. (2012). The yeast rapid tRNA decay pathway
competes with elongation factor 1A for substrate tRNAs and
acts on tRNAs lacking one or more of several modifications.
RNA 18 , 1886 – 1896.
Dez, C., Houseley, J., and Tollervey, D. (2006). Surveillance of
nuclear-restricted pre-ribosomes within a subnucleolar region
of Saccharomyces cerevisiae. EMBO J. 25 , 1534 – 1546.
Ding, Q., Markesbery, W.R., Chen, Q., Li, F., and Keller, J.N. (2005).
Ribosome dysfunction is an early event in Alzheimer ’ s disease.
J. Neurosci. 25 , 9171 – 9175.
Dong, H., Nilsson, L., and Kurland, C.G. (1995). Gratuitous overex-
pression of genes in Escherichia coli leads to growth inhibition
and ribosome destruction. J. Bacteriol. 177 , 1497 – 1504.
Ehrenberg, M., Bremer, H., and Dennis, P.P. (2013). Medium-
dependent control of the bacterial growth rate. Biochimie 95 ,
643 – 658.
El-Sharoud, W.M. (2004). Ribosome inactivation for preservation:
concepts and reservations. Sci. Prog. 87 , 137 – 152.
Frazier, A.D. and Champney, W.S. (2012). Impairment of ribosomal
subunit synthesis in aminoglycoside-treated ribonuclease
mutants of Escherichia coli. Arch. Microbiol. 194 , 1033 – 1041.
Freed, E.F., Bleichert, F., Dutca, L.M., and Baserga, S.J. (2010). When
ribosomes go bad: diseases of ribosome biogenesis. Mol.
Biosyst. 6 , 481 – 493.
Fujii, K., Kitabatake, M., Sakata, T., Miyata, A., and Ohno, M. (2009).
A role for ubiquitin in the clearance of nonfunctional rRNAs.
Genes Dev. 23 , 963 – 974.
Fujii, K., Sakata, T., Kitabatake, M., and Ohno, M. (2012). 40S
subunit dissociation and proteasome-dependent RNA
degradation in nonfunctional 25S rRNA decay. EMBO J. 31 ,
2579 – 2589.
Gausing, K. (1977). Regulation of ribosome production in
Escherichia coli: synthesis and stability of ribosomal RNA and
of ribosomal protein messenger RNA at different growth rates.
J. Mol. Biol. 115 , 335 – 354.
Gutgsell, N.S. and Jain, C. (2012). Role of precursor sequences in
the ordered maturation of E. coli 23S ribosomal RNA. RNA 18 ,
345 – 353.
H ä user, R., Pech, M., Kijek, J., Yamamoto, H., Titz, B., Naeve, F.,
Tovchigrechko, A., Yamamoto, K., Szaflarski, W., Takeuchi, N.,
et al. (2012). RsfA (YbeB) Proteins are conserved ribosomal
silencing factors. PLOS Genet. 8 , e1002815.
Henras, A.K., Soudet, J., G é rus, M., Lebaron, S., Caizergues-Ferrer,
M., Mougin, A., and Henry, Y. (2008). The post-transcriptional
steps of eukaryotic ribosome biogenesis. Cell. Mol. Life Sci.
65 , 2334 – 2359.
Hillwig, M.S., Contento, A.L., Meyer, A., Ebany, D., Bassham, D.C.,
and Macintosh, G.C. (2011). RNS2, a conserved member of
the RNase T2 family, is necessary for ribosomal RNA decay in
plants. Proc. Natl. Acad. Sci. USA 108 , 1093 – 1098.
Hoat, T.X., Nakayashiki, H., Tosa, Y., and Mayama, S. (2006).
Specific cleavage of ribosomal RNA and mRNA during victorin-
induced apoptotic cell death in oat. Plant J. 46 , 922 – 933.
Hsu, D., Shih, L.M., and Zee, Y.C. (1994). Degradation of rRNA in
Salmonella strains: a novel mechanism to regulate the concen-
trations of rRNA and ribosomes. J. Bacteriol. 176 , 4761 – 4765.
Jacob, A.I., K ö hrer, C., Davies, B.W., RajBhandary, U.L., and
Walker, G.C. (2013). Conserved bacterial RNase YbeY plays
key roles in 70S ribosome quality control and 16S rRNA
maturation. Mol. Cell 49 , 427 – 438.
Jia, J., Arif, A., Willard, B., Smith, J.D., Stuehr, D.J., Hazen, S.L., and
Fox, P.L. (2012). Protection of extraribosomal RPL13a by GAPDH
and dysregulation by S-nitrosylation. Mol. Cell 47 , 656 – 663.
Johnson, R.M., Evans, J.D., Robinson, G.E., and Berenbaum, M.R.
(2009). Changes in transcript abundance relating to colony
collapse disorder in honey bees (Apis mellifera). Proc. Natl.
Acad. Sci. USA 106 , 14790 – 14795.
Johnston, G.C., Singer, R.A., and McFarlane, S. (1977). Growth and
cell division during nitrogen starvation of the yeast Saccha-romyces cerevisiae. J. Bacteriol. 132 , 723 – 730.
Ju, Q. and Warner, J.R. (1994). Ribosome synthesis during the
growth cycle of Saccharomyces cerevisiae. Yeast 10 , 151 – 157.
Kaczanowska, M. and Ryden-Aulin, M. (2007). Ribosome biogenesis
and the translation process in Escherichia coli. Microbiol. Mol.
Biol. Rev. 71 , 477 – 494.
Kalpaxis, D.L., Karahalios, P., and Papapetropoulou, M. (1998).
Changes in ribosomal activity of Escherichia coli cells during
prolonged culture in sea salts medium. J. Bacteriol. 180 ,
3114 – 3119.
Kaplan, R. and Apirion, D. (1975). The fate of ribosomes in
Escherichia coli cells starved for a carbon source. J. Biol. Chem.
250 , 1854 – 1863.
Karbstein, K. (2013). Quality control mechanisms during ribosome
maturation. Trends Cell Biol., in press. DOI 10.1016/j.
tcb.2013.01.004.
King, K.L., Jewell, C.M., Bortner, C.D., and Cidlowski, J.A. (2000).
28S ribosome degradation in lymphoid cell apoptosis:
evidence for caspase and Bcl-2-dependent and -independent
pathways. Cell Death Differ. 7 , 994 – 1001.
Kitahara, K. and Miyazaki, K. (2011). Specific inhibition of bacterial
RNase T2 by helix 41 of 16S ribosomal RNA. Nat. Commun. 2 ,
549 – 547.
Kraft, C., Deplazes, A., Sohrmann, M., and Peter, M. (2008). Mature
ribosomes are selectively degraded upon starvation by an
autophagy pathway requiring the Ubp3p/Bre5p ubiquitin
protease. Nat. Cell Biol. 10 , 602 – 610.
Krokowski, D., Gaccioli, F., Majumder, M., Mullins, M.R., Yuan, C.L.,
Papadopoulou, B., Merrick, W.C., Komar, A.A., Taylor, D.J.,
Brought to you by | Tartu University LibraryAuthenticated
Download Date | 1/29/15 12:45 PM
854 Ü . Maiv ä li et al.: Ribosome degradation
and Hatzoglou, M. (2011). Characterization of hibernating
ribosomes in mammalian cells. Cell Cycle 10 , 2691 – 2702.
Kuroda, A., Murphy, H., Cashel, M., and Kornberg, A. (1997).
Guanosine tetra- and pentaphosphate promote accumulation
of inorganic polyphosphate in Escherichia coli. J. Biol. Chem.
272 , 21240 – 21243.
Kuroda, A., Tanaka, S., Ikeda, T., Kato, J., Takiguchi, N., and Ohtake, H.
(1999). Inorganic polyphosphate kinase is required to
stimulate protein degradation and for adaptation to amino acid
starvation in Escherichia coli. Proc. Natl. Acad. Sci. USA 96 ,
14264 – 14269.
Kuroda, A., Nomura, K., Ohtomo, R., Kato, J., Ikeda, T., Takiguchi,
N., Ohtake, H., and Kornberg, A. (2001). Role of inorganic
polyphosphate in promoting ribosomal protein degradation by
the Lon protease in E. coli. Science 293 , 705 – 708.
Lafontaine, D.L.J. (2010). A ‘ garbage can ’ for ribosomes: how
eukaryotes degrade their ribosomes. Trends Biochem. Sci. 35 ,
267 – 277.
LaRiviere, F.J., Cole, S.E., Ferullo, D.J., and Moore, M.J. (2006).
A late-acting quality control process for mature eukaryotic
rRNAs. Mol. Cell 24 , 619 – 626.
Lebaron, S., Schneider, C., van Nues, R.W., Swiatkowska, A., Walsh,
D., B ö ttcher, B., Granneman, S., Watkins, N.J., and Tollervey, D.
(2012). Proofreading of pre-40S ribosome maturation by a
translation initiation factor and 60S subunits. Nat. Struct. Mol.
Biol. 19 , 744 – 753.
Li, Z., Reimers, S., Pandit, S., and Deutscher, M.P. (2002). RNA
quality control: degradation of defective transfer RNA. EMBO J.
21 , 1132 – 1138.
Liang, W. and Deutscher, M.P. (2011). Post-translational modification
of RNase R is regulated by stress-dependent reduction in the
acetylating enzyme Pka (YfiQ). RNA 18 , 37 – 41.
Liang, W. and Deutscher, M.P. (2012a). Post-translational
modification of RNase R is regulated by stress-dependent
reduction in the acetylating enzyme Pka (YfiQ). RNA 18 , 37 – 41.
Liang, W. and Deutscher, M.P. (2012b). Transfer-messenger
RNA-SmpB protein regulates ribonuclease R turnover by
promoting binding of HslUV and lon proteases. J. Biol. Chem.
287 , 33472 – 33479.
Liu, M., Gong, X., Alluri, R.K., Wu, J., Sablo, T., and Li, Z. (2012).
Characterization of RNA damage under oxidative stress in
Escherichia coli. Biol. Chem. 393 , 123 – 132.
MacIntosh, G.C. (2011). RNase T2 family: enzymatic properties,
functional diversity, and evolution of ancient ribonucleases.
In: Ribonucleases, Nucleic Acids and Molecular Biology 26,
A.W. Nicholson, ed. (Springer-Verlag), pp. 89 – 114.
Maes, A., Gracia, C., Hajnsdorf, E., and R é gnier, P. (2011). Search for
poly(A) polymerase targets in E. coli reveals its implication in
surveillance of Glu tRNA processing and degradation of stable
RNAs. Mol. Microbiol. 83 , 436 – 451.
Metodiev, M.D., Lesko, N., Park, C.B., Amara, Y., Shi, Y., Wibom, R.,
Hultenby, K., Gustafsson, C.M., and Larsson, N.-G. (2009).
Methylation of 12S rRNA is necessary for in vivo stability of the
small subunit of the mammalian mitochondrial ribosome. Cell
Metab. 9 , 386 – 397.
Molin, S., Von Meyenburg, K., Maaloe, O., Hansen, M.T., and Pato,
M.L. (1977). Control of ribosome synthesis in Escherichia coli: analysis of an energy source shift-down. J. Bacteriol. 131 , 7 – 17.
Moll, I. and Engelberg-Kulka, H. (2012). Selective translation during
stress in Escherichia coli . Trends Biochem. Sci. 37 , 493 – 498.
Mroczek, S. and Kufel, J. (2008). Apoptotic signals induce specific
degradation of ribosomal RNA in yeast. Nucleic Acids Res. 36 ,
2874 – 2888.
Nanamiya, H., Akanuma, G., Natori, Y., Murayama, R., Kosono, S.,
Kudo, T., Kobayashi, K., Ogasawara, N., Park, S.-M., Ochi, K.,
et al. (2004). Zinc is a key factor in controlling alternation of
two types of L31 protein in the Bacillus subtilis ribosome. Mol.
Microbiol. 52 , 273 – 283.
Narla, A. and Ebert, B.L. (2010). Ribosomopathies: human disorders
of ribosome dysfunction. Blood 115 , 3196 – 3205.
Nierhaus, K.H. and Dohme, F. (1974). Total reconstitution of
functionally active 50S ribosomal subunits from Escherichia coli. Proc. Natl. Acad. Sci. USA 71 , 4713 – 4717.
Nunomura, A., Moreira, P.I., Castellani, R.J., Lee, H.-G., Zhu, X.,
Smith, M.A., and Perry, G. (2012). Oxidative damage to RNA
in aging and neurodegenerative disorders. Neurotox. Res. 22 ,
231 – 248.
Nusspaumer, G., Remacha, M., and Ballesta, J.P. (2000). Phospho-
rylation and N-terminal region of yeast ribosomal protein P1
mediate its degradation, which is prevented by protein P2.
EMBO J. 19 , 6075 – 6084.
Ougland, R., Zhang, C.-M., Liiv, A., Johansen, R.F., Seeberg, E.,
Hou, Y.-M., Remme, J., and Falnes, P. Ø . (2004). AlkB restores
the biological function of mRNA and tRNA inactivated by
chemical methylation. Mol. Cell 16 , 107 – 116.
Panse, V.G. and Johnson, A.W. (2010). Maturation of eukaryotic
ribosomes: acquisition of functionality. Trends Biochem. Sci.
35 , 260 – 266.
Pestov, D.G. and Shcherbik, N. (2012). Rapid cytoplasmic turnover
of yeast ribosomes in response to rapamycin inhibition of TOR.
Mol. Cell. Biol. 32 , 2135 – 2144.
Piir, K., Paier, A., Liiv, A., Tenson, T., and Maivali, U. (2011).
Ribosome degradation in growing bacteria. EMBO Rep. 12 ,
458 – 462.
Polikanov, Y.S., Blaha, G.M., and Steitz, T.A. (2012). How hibernation
factors RMF, HPF, and YfiA turn off protein synthesis. Science
336 , 915 – 918.
Pulk, A., Liiv, A., Peil, L., Maivali, U., Nierhaus, K., and Remme, J.
(2010). Ribosome reactivation by replacement of damaged
proteins. Mol. Microbiol. 75 , 801 – 814.
Ramagopal, S. and Subramanian, A.R. (1974). Alteration in the
acetylation level of ribosomal protein L12 during growth
cycle of Escherichia coli. Proc. Natl. Acad. Sci. USA 71 ,
2136 – 2140.
Scott, M., Gunderson, C.W., Mateescu, E.M., Zhang, Z., and Hwa, T.
(2010). Interdependence of cell growth and gene expression:
origins and consequences. Science 330 , 1099 – 1102.
Shajani, Z., Sykes, M.T., and Williamson, J.R. (2011). Assembly of
bacterial ribosomes. Annu. Rev. Biochem. 80 , 501 – 526.
Shcherbik, N. and Pestov, D.G. (2011). The ubiquitin ligase Rsp5 is
required for ribosome stability in Saccharomyces cerevisiae.
RNA 17 , 1422 – 1428.
Silvers, J.A. and Champney, W.S. (2005). Accumulation and
turnover of 23S ribosomal RNA in azithromycin-inhibited
ribonuclease mutant strains of Escherichia coli. Arch.
Microbiol. 184 , 66 – 77.
Slomovic, S., Fremder, E., Staals, R.H.G., Pruijn, G.J.M., and
Schuster, G. (2010). Addition of poly(A) and poly(A)-rich tails
during RNA degradation in the cytoplasm of human cells. Proc.
Natl. Acad. Sci. USA 107 , 7407 – 7412.
Brought to you by | Tartu University LibraryAuthenticated
Download Date | 1/29/15 12:45 PM
Ü . Maiv ä li et al.: Ribosome degradation 855
Strunk, B.S., Novak, M.N., Young, C.L., and Karbstein, K. (2012).
A translation-like cycle is a quality control checkpoint for
maturing 40S ribosome subunits. Cell 150 , 111 – 121.
Thompson, D.M. and Parker, R. (2009). Stressing out over tRNA
cleavage. Cell 138 , 215 – 219.
Tsai, Y.C., Du, D., Dominguez-Malfavon, L., Dimastrogiovanni, D.,
Cross, J., Callaghan, A.J., Garcia-Mena, J., and Luisi, B.F. (2012).
Recognition of the 70S ribosome and polysome by the RNA degra-
dosome in Escherichia coli. Nucleic Acids Res. 40, 10417–10431.
Tsuboi, T., Kuroha, K., Kudo, K., Makino, S., Inoue, E., Kashima, I.,
and Inada, T. (2012). Dom34:hbs1 plays a general role in
quality-control systems by dissociation of a stalled ribosome at
the 3 ′ end of aberrant mRNA. Mol. Cell 46 , 518 – 529.
Van Dyke, N., Chanchorn, E., and Van Dyke, M.W. (2013). The
Saccharomyces cerevisiae protein Stm1p facilitates ribosome
preservation during quiescence. Biochem. Biophys. Res. Com.
430 , 745 – 750.
Vesper, O., Amitai, S., Belitsky, M., Byrgazov, K., Kaberdina, A.C.,
Engelberg-Kulka, H., and Moll, I. (2011). Selective translation of
leaderless mRNAs by specialized ribosomes generated by MazF
in Escherichia coli. Cell 147 , 147 – 157.
Wada, A. (1998). Growth phase coupled modulation of Escherichia coli ribosomes. Genes Cells 3 , 203 – 208.
Wada, A., Mikkola, R., Kurland, C.G., and Ishihama, A. (2000).
Growth phase-coupled changes of the ribosome profile in
natural isolates and laboratory strains of Escherichia coli. J. Bacteriol. 182 , 2893 – 2899.
Warner, J.R. (1999). The economics of ribosome biosynthesis in
yeast. Trends Biochem. Sci. 24 , 437 – 440.
Wilusz, J.E., Whipple, J.M., Phizicky, E.M., and Sharp, P.A. (2011).
tRNAs marked with CCACCA are targeted for degradation.
Science 334 , 817 – 821.
Wu, J. and Li, Z. (2008). Human polynucleotide phosphorylase
reduces oxidative RNA damage and protects HeLa cell against
oxidative stress. Biochem. Biophys. Res. Commun. 372 ,
288 – 292.
Wu, J., Jiang, Z., Liu, M., Gong, X., Wu, S., Burns, C.M., and Li, Z.
(2009). Polynucleotide phosphorylase protects Escherichia
coli against oxidative stress. Biochemistry 48 , 2012 – 2020.
Yoshida, H., Maki, Y., Furuike, S., Sakai, A., Ueta, M., and Wada,
A. (2012). YqjD is an inner membrane protein associated with
stationary-phase ribosomes in Escherichia coli. J. Bacteriol.
194 , 4178 – 4183.
Zhou, Z. and Deutscher, M.P. (1997). An essential function for
the phosphate-dependent exoribonucleases RNase PH
and polynucleotide phosphorylase. J. Bacteriol. 179 ,
4391 – 4395.
Zundel, M.A., Basturea, G.N., and Deutscher, M.P. (2009). Initiation
of ribosome degradation during starvation in Escherichia coli. RNA 15 , 977 – 983.
Ülo Maiväli is a molecular biologist studying ribosomal metabolism
in Escherichia coli . He obtained his PhD from the University of Tartu
in 2004. Currently he is a researcher in the Institute of Technology,
University of Tartu, Estonia.
Anton Paier has a Master’s degree in Modern Literature from the
University of Genua, Italy, a Bachelor’s in Military History from the
University of Stockholm and a Master’s in Biomedical Laboratory
Sciences from the Karolinska Institute (2008). Currently he is doing
a PhD in Molecular Biology at the University of Tartu. His thesis is
centered on the ribosomal degradation in E. coli .
Tanel Tenson is a biochemist and microbiologist studying the
mechanisms of antibiotic action and antibiotic resistance. He
obtained his PhD from the University of Tartu in 1997. Tanel Tenson
is currently Professor of Technology of Antimicrobial Compounds at
the Institute of Technology, University of Tartu.
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