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.
Exosome-Mediated Recognition and Degradation of mRNAs Lacking a Termination Codon
Ambro van Hoof,12*Pamela A. Frischmeyer,13Harry C. Dietz,13Roy 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 terminationcodons are
unstable in eukaryotic cells. We used yeast mutantsto demonstrate that
these "nonstop" mRNAs are degraded by theexosome in a 3'-to-5'
direction. The degradation of nonstop transcriptsrequires the
exosome-associated protein Ski7p. Ski7p is closelyrelated to the
translation elongation factor EF1A and the translationtermination
factor eRF3. This suggests that the recognition ofnonstop mRNAs
involves the binding of Ski7p to an empty aminoacyl-(RNA-binding)site
(A site) on the ribosome, thereby bringing the exosome toa mRNA with a
ribosome stalled near the 3' end. This system efficientlydegrades
mRNAs that are prematurely polyadenylated within thecoding 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.)
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Lynne E. Maquat (22 March 2002) Science295 (5563), 2221.
[DOI: 10.1126/science.1071285] |Summary »|Full Text »|PDF »
REPORTS
Pamela A. Frischmeyer, Ambro van Hoof, Kathryn O'Donnell, Anthony L. Guerrerio, Roy Parker, and Harry C. Dietz (22 March 2002) Science295 (5563), 2258.
[DOI: 10.1126/science.1067338] |Abstract »|Full Text »|PDF »
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.
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.
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.
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.
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.
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.
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.