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PMID: 10882133 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Interaction between a poly(A)-specific ribonuclease and the 5' cap influences mRNA deadenylation rates in vitro.

Molecular cell ·Vol. 5 ·No. 3 ·2000-03-00 ·Pages 479-88

Gao M, Fritz DT, Ford LP, Wilusz J

Abstract

We have used an in vitro system that reproduces in vivo aspects of mRNA turnover to elucidate mechanisms of deadenylation. DAN, the major enzyme responsible for poly(A) tail shortening in vitro, specifically interacts with the 5' cap structure of RNA substrates, and this interaction is greatly stimulated by a poly(A) tail. Several observations suggest that cap-DAN interactions are functionally important for the networking between regulated mRNA stability and translation. First, uncapped RNA substrates are inefficiently deadenylated. Second, a stem-loop structure in the 5' UTR dramatically reduces deadenylation by interfering with cap-DAN interactions. Third, the addition of cap binding protein eIF4E inhibits deadenylation in vitro. These data provide insights into the early steps of substrate recognition that target an mRNA for degradation.

MeSH Terms
Eukaryotic Initiation Factor-4E Exoribonucleases/drug effects,metabolism Models, Theoretical Peptide Initiation Factors/metabolism Poly A/metabolism Protein Binding Proteins/drug effects,metabolism RNA Cap Analogs/pharmacology RNA Caps/metabolism RNA Stability RNA, Messenger/metabolism Subcellular Fractions/enzymology Substrate Specificity
Chemicals
Eukaryotic Initiation Factor-4E Peptide Initiation Factors Proteins RNA Cap Analogs RNA Caps RNA, Messenger Poly A Exoribonucleases poly(A)-specific ribonuclease
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Gao M
Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103, USA.
Fritz D T
Ford L P
Wilusz J
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-2765
DOI
10.1016/s1097-2765(00)80442-6
Published
2000-03-00
Pages
479-88
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC2811581
Subset
IM
Grants
NCI NIH HHS · R01 CA080062-01A1 · United States
NCI NIH HHS · CA09665 · United States
NCI NIH HHS · R01 CA080062-02 · United States
NCI NIH HHS · T32 CA009665 · United States
NCI NIH HHS · CA80062 · United States
NIGMS NIH HHS · GM56434 · United States
External Links
PubMed source DOI: 10.1016/s1097-2765(00)80442-6 PMC Full Text View journal details
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