Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 22 March 2002:
Vol. 295. no. 5563, pp. 2262 - 2264
DOI: 10.1126/science.1067272
Prev | Table of Contents | Next

Reports

Exosome-Mediated Recognition and Degradation of mRNAs Lacking a Termination Codon

Ambro van Hoof,12* Pamela A. Frischmeyer,13 Harry C. Dietz,13 Roy Parker12*

One role of messenger RNA (mRNA) degradation is to maintain the fidelity of gene expression by degrading aberrant transcripts. Recent results show that mRNAs without translation termination codons are unstable in eukaryotic cells. We used yeast mutants to demonstrate that these "nonstop" mRNAs are degraded by the exosome in a 3'-to-5' direction. The degradation of nonstop transcripts requires the exosome-associated protein Ski7p. Ski7p is closely related to the translation elongation factor EF1A and the translation termination factor eRF3. This suggests that the recognition of nonstop mRNAs involves the binding of Ski7p to an empty aminoacyl-(RNA-binding) site (A site) on the ribosome, thereby bringing the exosome to a mRNA with a ribosome stalled near the 3' end. This system efficiently degrades mRNAs that are prematurely polyadenylated within the coding region and prevents their expression.

1 Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA.
2 University of Arizona, Department of Molecular and Cellular Biology, Tucson, AZ 85721, USA.
3 Johns Hopkins University, Institute for Genetic Medicine, School of Medicine, Baltimore, MD 21205, USA.
*   To whom correspondence should be addressed. E-mail: ambro{at}u.arizona.edu (A.v.H.) or rrparker{at}u.arizona.edu (R.P.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Polypyrimidine Tract Binding Protein Prevents Activity of an Intronic Regulatory Element That Promotes Usage of a Composite 3'-Terminal Exon.
V. Anquetil, C. Le Sommer, A. Mereau, S. Hamon, H. Lerivray, and S. Hardy (2009)
J. Biol. Chem. 284, 32370-32383
   Abstract »    Full Text »    PDF »
The role of deadenylation in the degradation of unstable mRNAs in trypanosomes.
A. Schwede, T. Manful, B. A. Jha, C. Helbig, N. Bercovich, M. Stewart, and C. Clayton (2009)
Nucleic Acids Res. 37, 5511-5528
   Abstract »    Full Text »    PDF »
Unconventional splicing of XBP1 mRNA occurs in the cytoplasm during the mammalian unfolded protein response.
A. Uemura, M. Oku, K. Mori, and H. Yoshida (2009)
J. Cell Sci. 122, 2877-2886
   Abstract »    Full Text »    PDF »
Human Mitochondrial SUV3 and Polynucleotide Phosphorylase Form a 330-kDa Heteropentamer to Cooperatively Degrade Double-stranded RNA with a 3'-to-5' Directionality.
D. D.-H. Wang, Z. Shu, S. A. Lieser, P.-L. Chen, and W.-H. Lee (2009)
J. Biol. Chem. 284, 20812-20821
   Abstract »    Full Text »    PDF »
Analysis of Dom34 and Its Function in No-Go Decay.
D. O. Passos, M. K. Doma, C. J. Shoemaker, D. Muhlrad, R. Green, J. Weissman, J. Hollien, and R. Parker (2009)
Mol. Biol. Cell 20, 3025-3032
   Abstract »    Full Text »    PDF »
Analysis of nonstop mRNA translation in the absence of tmRNA in Escherichia coli.
K. Kuroha, N. Horiguchi, H. Aiba, and T. Inada (2009)
Genes Cells 14, 739-749
   Abstract »    Full Text »    PDF »
Origins and activities of the eukaryotic exosome.
S. Lykke-Andersen, D. E. Brodersen, and T. H. Jensen (2009)
J. Cell Sci. 122, 1487-1494
   Abstract »    Full Text »    PDF »
Nascent Peptide-dependent Translation Arrest Leads to Not4p-mediated Protein Degradation by the Proteasome.
L. N. Dimitrova, K. Kuroha, T. Tatematsu, and T. Inada (2009)
J. Biol. Chem. 284, 10343-10352
   Abstract »    Full Text »    PDF »
A role for ubiquitin in the clearance of nonfunctional rRNAs.
K. Fujii, M. Kitabatake, T. Sakata, A. Miyata, and M. Ohno (2009)
Genes & Dev. 23, 963-974
   Abstract »    Full Text »    PDF »
Evidence for core exosome independent function of the nuclear exoribonuclease Rrp6p.
K. P. Callahan and J. S. Butler (2008)
Nucleic Acids Res. 36, 6645-6655
   Abstract »    Full Text »    PDF »
Depurination of Brome Mosaic Virus RNA3 in Vivo Results in Translation-dependent Accelerated Degradation of the Viral RNA.
R. Gandhi, M. Manzoor, and K. A. Hudak (2008)
J. Biol. Chem. 283, 32218-32228
   Abstract »    Full Text »    PDF »
Codon Optimization Increases Steady-State mRNA Levels in Aspergillus oryzae Heterologous Gene Expression.
M. Tokuoka, M. Tanaka, K. Ono, S. Takagi, T. Shintani, and K. Gomi (2008)
Appl. Envir. Microbiol. 74, 6538-6546
   Abstract »    Full Text »    PDF »
Poly(rC) Binding Proteins and the 5' Cloverleaf of Uncapped Poliovirus mRNA Function during De Novo Assembly of Polysomes.
B. J. Kempf and D. J. Barton (2008)
J. Virol. 82, 5835-5846
   Abstract »    Full Text »    PDF »
Structure of Yeast Dom34: A PROTEIN RELATED TO TRANSLATION TERMINATION FACTOR Erf1 AND INVOLVED IN No-Go DECAY.
M. Graille, M. Chaillet, and H. van Tilbeurgh (2008)
J. Biol. Chem. 283, 7145-7154
   Abstract »    Full Text »    PDF »
Recessive black Is Allelic to the yellow Plumage Locus in Japanese Quail and Associated With a Frameshift Deletion in the ASIP Gene.
T. Hiragaki, M. Inoue-Murayama, M. Miwa, A. Fujiwara, M. Mizutani, F. Minvielle, and S. Ito (2008)
Genetics 178, 771-775
   Abstract »    Full Text »    PDF »
Messenger RNA Surveillance Systems Monitoring Proper Translation Termination.
N. Akimitsu (2008)
J. Biochem. 143, 1-8
   Abstract »    Full Text »    PDF »
Mechanism of mRNA deadenylation: evidence for a molecular interplay between translation termination factor eRF3 and mRNA deadenylases.
Y. Funakoshi, Y. Doi, N. Hosoda, N. Uchida, M. Osawa, I. Shimada, M. Tsujimoto, T. Suzuki, T. Katada, and S.-i. Hoshino (2007)
Genes & Dev. 21, 3135-3148
   Abstract »    Full Text »    PDF »
Architecture of the yeast Rrp44 exosome complex suggests routes of RNA recruitment for 3' end processing.
H.-W. Wang, J. Wang, F. Ding, K. Callahan, M. A. Bratkowski, J. S. Butler, E. Nogales, and A. Ke (2007)
PNAS 104, 16844-16849
   Abstract »    Full Text »    PDF »
A Genomic Screen in Yeast Reveals Novel Aspects of Nonstop mRNA Metabolism.
M. A. Wilson, S. Meaux, and A. van Hoof (2007)
Genetics 177, 773-784
   Abstract »    Full Text »    PDF »
The PMC2NT domain of the catalytic exosome subunit Rrp6p provides the interface for binding with its cofactor Rrp47p, a nucleic acid-binding protein.
J. A. Stead, J. L. Costello, M. J. Livingstone, and P. Mitchell (2007)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function.
O. Isken and L. E. Maquat (2007)
Genes & Dev. 21, 1833-3856
   Abstract »    Full Text »    PDF »
Mutational analysis of a viral RNA element that counteracts rapid RNA decay by interaction with the polyadenylate tail.
N. K. Conrad, M.-D. Shu, K. E. Uyhazi, and J. A. Steitz (2007)
PNAS 104, 10412-10417
   Abstract »    Full Text »    PDF »
INCREASED SIZE EXCLUSION LIMIT2 Encodes a Putative DEVH Box RNA Helicase Involved in Plasmodesmata Function during Arabidopsis Embryogenesis.
K. Kobayashi, M. S. Otegui, S. Krishnakumar, M. Mindrinos, and P. Zambryski (2007)
PLANT CELL 19, 1885-1897
   Abstract »    Full Text »    PDF »
An Archaeal Protein with Homology to the Eukaryotic Translation Initiation Factor 5A Shows Ribonucleolytic Activity.
S. Wagner and G. Klug (2007)
J. Biol. Chem. 282, 13966-13976
   Abstract »    Full Text »    PDF »
Translation of the poly(A) tail plays crucial roles in nonstop mRNA surveillance via translation repression and protein destabilization by proteasome in yeast.
S. Ito-Harashima, K. Kuroha, T. Tatematsu, and T. Inada (2007)
Genes & Dev. 21, 519-524
   Abstract »    Full Text »    PDF »
The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA.
X. Guo, J. Ma, J. Sun, and G. Gao (2007)
PNAS 104, 151-156
   Abstract »    Full Text »    PDF »
Mammalian dap3 is an essential gene required for mitochondrial homeostasis in vivo and contributing to the extrinsic pathway for apoptosis.
H.-R. Kim, H.-J. Chae, M. Thomas, T. Miyazaki, A. Monosov, E. Monosov, M. Krajewska, S. Krajewski, and J. C. Reed (2007)
FASEB J 21, 188-196
   Abstract »    Full Text »    PDF »
Mutant LYS2 mRNAs retained and degraded in the nucleus of Saccharomyces cerevisiae.
B. Das, S. Das, and F. Sherman (2006)
PNAS 103, 10871-10876
   Abstract »    Full Text »    PDF »
Tpa1p Is Part of an mRNP Complex That Influences Translation Termination, mRNA Deadenylation, and mRNA Turnover in Saccharomyces cerevisiae..
K. M. Keeling, J. Salas-Marco, L. Z. Osherovich, and D. M. Bedwell (2006)
Mol. Cell. Biol. 26, 5237-5248
   Abstract »    Full Text »    PDF »
Yeast transcripts cleaved by an internal ribozyme provide new insight into the role of the cap and poly(A) tail in translation and mRNA decay.
S. Meaux and A. Van Hoof (2006)
RNA 12, 1323-1337
   Abstract »    Full Text »    PDF »
MicroRNAs: New players in an old game..
M. Gupta and G. Brewer (2006)
PNAS 103, 3951-3952
   Full Text »    PDF »
Differential Distribution of Exosome Subunits at the Nuclear Lamina and in Cytoplasmic Foci.
A. C. Graham, D. L. Kiss, and E. D. Andrulis (2006)
Mol. Biol. Cell 17, 1399-1409
   Abstract »    Full Text »    PDF »
Accumulation of unstable promoter-associated transcripts upon loss of the nuclear exosome subunit Rrp6p in Saccharomyces cerevisiae.
C. A. Davis and M. Ares Jr. (2006)
PNAS 103, 3262-3267
   Abstract »    Full Text »    PDF »
Identification of Functionally Important Amino Acids of Ribosomal Protein L3 by Saturation Mutagenesis.
A. Meskauskas, A. N. Petrov, and J. D. Dinman (2005)
Mol. Cell. Biol. 25, 10863-10874
   Abstract »    Full Text »    PDF »
Conserved Functions of Yeast Genes Support the Duplication, Degeneration and Complementation Model for Gene Duplication.
A. van Hoof (2005)
Genetics 171, 1455-1461
   Abstract »    Full Text »    PDF »
A Nuclear Surveillance Pathway for mRNAs with Defective Polyadenylation.
L. Milligan, C. Torchet, C. Allmang, T. Shipman, and D. Tollervey (2005)
Mol. Cell. Biol. 25, 9996-10004
   Abstract »    Full Text »    PDF »
PACdb: PolyA Cleavage Site and 3'-UTR Database.
J. M. Brockman, P. Singh, D. Liu, S. Quinlan, J. Salisbury, and J. H. Graber (2005)
Bioinformatics 21, 3691-3693
   Abstract »    Full Text »    PDF »
Domain interactions within the Ski2/3/8 complex and between the Ski complex and Ski7p.
L. WANG, M. S. LEWIS, and A. W. JOHNSON (2005)
RNA 11, 1291-1302
   Abstract »    Full Text »    PDF »
Genetic interactions between [PSI+] and nonstop mRNA decay affect phenotypic variation.
M. A. Wilson, S. Meaux, R. Parker, and A. van Hoof (2005)
PNAS 102, 10244-10249
   Abstract »    Full Text »    PDF »
Heptameric (L12)6/L10 rather than canonical pentameric complexes are found by tandem MS of intact ribosomes from thermophilic bacteria.
L. L. Ilag, H. Videler, A. R. McKay, F. Sobott, P. Fucini, K. H. Nierhaus, and C. V. Robinson (2005)
PNAS 102, 8192-8197
   Abstract »    Full Text »    PDF »
Metabolic Engineering in the -omics Era: Elucidating and Modulating Regulatory Networks.
G. N. Vemuri and A. A. Aristidou (2005)
Microbiol. Mol. Biol. Rev. 69, 197-216
   Abstract »    Full Text »    PDF »
Pre-mRNA processing enhancer (PPE) elements from intronless genes play additional roles in mRNA biogenesis than do ones from intron-containing genes.
S. Guang and J. E. Mertz (2005)
Nucleic Acids Res. 33, 2215-2226
   Abstract »    Full Text »    PDF »
Decay of mRNAs targeted by RISC requires XRN1, the Ski complex, and the exosome.
T. I. ORBAN and E. IZAURRALDE (2005)
RNA 11, 459-469
   Abstract »    Full Text »    PDF »
The Nuclear Exosome Contributes to Autogenous Control of NAB2 mRNA Levels.
K. M. Roth, M. K. Wolf, M. Rossi, and J. S. Butler (2005)
Mol. Cell. Biol. 25, 1577-1585
   Abstract »    Full Text »    PDF »
Under the Tucson sun: A meeting in the desert on mRNA decay.
K. E. BAKER and C. CONDON (2004)
RNA 10, 1680-1691
   Full Text »    PDF »
UNR, a new partner of poly(A)-binding protein, plays a key role in translationally coupled mRNA turnover mediated by the c-fos major coding-region determinant.
T.-C. Chang, A. Yamashita, C.-Y. A. Chen, Y. Yamashita, W. Zhu, S. Durdan, A. Kahvejian, N. Sonenberg, and A.-B. Shyu (2004)
Genes & Dev. 18, 2010-2023
   Abstract »    Full Text »    PDF »
mRNA deadenylation by PARN is essential for embryogenesis in higher plants.
S. V. REVERDATTO, J. A. DUTKO, J. A. CHEKANOVA, D. A. HAMILTON, and D. A. BELOSTOTSKY (2004)
RNA 10, 1200-1214
   Abstract »    Full Text »    PDF »
Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae.
S. Kadaba, A. Krueger, T. Trice, A. M. Krecic, A. G. Hinnebusch, and J. Anderson (2004)
Genes & Dev. 18, 1227-1240
   Abstract »    Full Text »    PDF »
Cytoplasmic foci are sites of mRNA decay in human cells.
N. Cougot, S. Babajko, and B. Seraphin (2004)
J. Cell Biol. 165, 31-40
   Abstract »    Full Text »    PDF »
RNase MRP Cleaves the CLB2 mRNA To Promote Cell Cycle Progression: Novel Method of mRNA Degradation.
T. Gill, T. Cai, J. Aulds, S. Wierzbicki, and M. E. Schmitt (2004)
Mol. Cell. Biol. 24, 945-953
   Abstract »    Full Text »    PDF »
The GPR54 Gene as a Regulator of Puberty.
S. B. Seminara, S. Messager, E. E. Chatzidaki, R. R. Thresher, J. S. Acierno Jr., J. K. Shagoury, Y. Bo-Abbas, W. Kuohung, K. M. Schwinof, A. G. Hendrick, et al. (2003)
N. Engl. J. Med. 349, 1614-1627
   Abstract »    Full Text »    PDF »
DcpS can act in the 5'-3' mRNA decay pathway in addition to the 3'-5' pathway.
E. van Dijk, H. Le Hir, and B. Seraphin (2003)
PNAS 100, 12081-12086
   Abstract »    Full Text »    PDF »
Investigation of a pathogenic mtDNA microdeletion reveals a translation-dependent deadenylation decay pathway in human mitochondria.
R. J. Temperley, S. H. Seneca, K. Tonska, E. Bartnik, L. A. Bindoff, R. N. Lightowlers, and Z. M.A. Chrzanowska-Lightowlers (2003)
Hum. Mol. Genet. 12, 2341-2348
   Abstract »    Full Text »    PDF »
Contribution of domain structure to the RNA 3' end processing and degradation functions of the nuclear exosome subunit Rrp6p.
S. PHILLIPS and J. S. BUTLER (2003)
RNA 9, 1098-1107
   Abstract »    Full Text »    PDF »
Degradation of Normal mRNA in the Nucleus of Saccharomyces cerevisiae.
B. Das, J. S. Butler, and F. Sherman (2003)
Mol. Cell. Biol. 23, 5502-5515
   Abstract »    Full Text »    PDF »
SsrA-mediated trans-translation plays a role in mRNA quality control by facilitating degradation of truncated mRNAs.
Y. YAMAMOTO, T. SUNOHARA, K. JOJIMA, T. INADA, and H. AIBA (2003)
RNA 9, 408-418
   Abstract »    Full Text »    PDF »
Novel Gene Product of Thogoto Virus Segment 6 Codes for an Interferon Antagonist.
K. Hagmaier, S. Jennings, J. Buse, F. Weber, and G. Kochs (2003)
J. Virol. 77, 2747-2752
   Abstract »    Full Text »    PDF »
Identification of a Human Decapping Complex Associated with hUpf Proteins in Nonsense-Mediated Decay.
J. Lykke-Andersen (2002)
Mol. Cell. Biol. 22, 8114-8121
   Abstract »    Full Text »    PDF »
A Peptide Chain Release Factor 2 Affects the Stability of UGA-Containing Transcripts in Arabidopsis Chloroplasts.
J. Meurer, L. Lezhneva, K. Amann, M. Godel, S. Bezhani, I. Sherameti, and R. Oelmuller (2002)
PLANT CELL 14, 3255-3269
   Abstract »    Full Text »    PDF »
From the Cover: The hDcp2 protein is a mammalian mRNA decapping enzyme.
Z. Wang, X. Jiao, A. Carr-Schmid, and M. Kiledjian (2002)
PNAS 99, 12663-12668
   Abstract »    Full Text »    PDF »
An mRNA Surveillance Mechanism That Eliminates Transcripts Lacking Termination Codons.
P. A. Frischmeyer, A. van Hoof, K. O'Donnell, A. L. Guerrerio, R. Parker, and H. C. Dietz (2002)
Science 295, 2258-2261
   Abstract »    Full Text »    PDF »
mRNA surveillance: the perfect persist.
E. Wagner and J. Lykke-Andersen (2002)
J. Cell Sci. 115, 3033-3038
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)