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PMID: 11782436 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The mammalian exosome mediates the efficient degradation of mRNAs that contain AU-rich elements.

The EMBO journal ·Vol. 21 ·No. 1-2 ·2002-01-15 ·Pages 165-74

Mukherjee D, Gao M, O'Connor JP, Raijmakers R, Pruijn G, Lutz CS, Wilusz J

Abstract

HeLa cytoplasmic extracts contain both 3'-5' and 5'-3' exonuclease activities that may play important roles in mRNA decay. Using an in vitro RNA deadenylation/decay assay, mRNA decay intermediates were trapped using phosphothioate-modified RNAs. These data indicate that 3'-5' exonucleolytic decay is the major pathway of RNA degradation following deadenylation in HeLa cytoplasmic extracts. Immunodepletion using antibodies specific for the exosomal protein PM-Scl75 demonstrated that the human exosome complex is required for efficient 3'-5' exonucleolytic decay. Furthermore, 3'-5' exonucleolytic decay was stimulated dramatically by AU-rich instability elements (AREs), implicating a role for the exosome in the regulation of mRNA turnover. Finally, PM-Scl75 protein was found to interact specifically with AREs. These data suggest that the interaction between the exosome and AREs plays a key role in regulating the efficiency of ARE-containing mRNA turnover.

MeSH Terms
Base Composition Base Sequence Cytoplasm/metabolism Exodeoxyribonuclease V Exodeoxyribonucleases/metabolism HeLa Cells Humans Models, Biological Mutation RNA Stability RNA, Messenger/chemistry,genetics,metabolism Tumor Necrosis Factor-alpha/genetics
Chemicals
RNA, Messenger Tumor Necrosis Factor-alpha Exodeoxyribonucleases Exodeoxyribonuclease V
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Mukherjee Devi
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.
Gao Min
O'Connor J Patrick
Raijmakers Reinout
Pruijn Ger
Lutz Carol S
Wilusz Jeffrey
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/21.1.165
Published
2002-01-15
Pages
165-74
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125812
Subset
IM
Grants
NCI NIH HHS · CA80062 · United States
External Links
PubMed source DOI: 10.1093/emboj/21.1.165 PMC Full Text View journal details
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