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PMID: 15314026 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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.

Genes & development ·Vol. 18 ·No. 16 ·2004-08-15 ·Pages 2010-23

Chang TC, Yamashita A, Chen CY, Yamashita Y, Zhu W, Durdan S, Kahvejian A, Sonenberg N, Shyu AB

Abstract

Messenger RNA decay mediated by the c-fos major protein coding-region determinant of instability (mCRD) is a useful system for studying translationally coupled mRNA turnover. Among the five mCRD-associated proteins identified previously, UNR was found to be an mCRD-binding protein and also a PABP-interacting protein. Interaction between UNR and PABP is necessary for the full destabilization function of the mCRD. By testing different classes of mammalian poly(A) nucleases, we identified CCR4 as a poly(A) nuclease involved in the mCRD-mediated rapid deadenylation in vivo and also associated with UNR. Blocking either translation initiation or elongation greatly impeded poly(A) shortening and mRNA decay mediated by the mCRD, demonstrating that the deadenylation step is coupled to ongoing translation of the message. These findings suggest a model in which the mCRD/UNR complex serves as a "landing/assembly" platform for formation of a deadenylation/decay mRNA-protein complex on an mCRD-containing transcript. The complex is dormant prior to translation. Accelerated deadenylation and decay of the transcript follows ribosome transit through the mCRD. This study provides new insights into a mechanism by which interplay between mRNA turnover and translation determines the lifespan of an mCRD-containing mRNA in the cytoplasm.

MeSH Terms
Animals Base Sequence Binding Sites Genes, fos Mice Molecular Sequence Data NIH 3T3 Cells Poly(A)-Binding Proteins/chemistry,genetics,metabolism,physiology Protein Biosynthesis RNA, Messenger/metabolism Receptors, CCR4 Receptors, Chemokine/metabolism Sequence Homology, Nucleic Acid
Chemicals
Ccr4 protein, mouse Poly(A)-Binding Proteins RNA, Messenger Receptors, CCR4 Receptors, Chemokine UNR protein, mouse
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Chang Tsung-Cheng
Department of Biochemistry and Molecular Biology, The University of Texas Medical School, Houston 77030, USA.
Yamashita Akio
Chen Chyi-Ying A
Yamashita Yukiko
Zhu Wenmiao
Durdan Simon
Kahvejian Avak
Sonenberg Nahum
Shyu Ann-Bin
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1219104
Published
2004-08-15
Pages
2010-23
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC514181
Subset
IM
Grants
NIGMS NIH HHS · R01 GM046454 · United States
NIGMS NIH HHS · GM 46454 · United States
NIGMS NIH HHS · GM 59211 · United States
External Links
PubMed source DOI: 10.1101/gad.1219104 PMC Full Text View journal details
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