Journal
EMBO JOURNAL
Volume 21, Issue 1-2, Pages 165-174Publisher
NATURE PUBLISHING GROUP
DOI: 10.1093/emboj/21.1.165
Keywords
AU-rich elements; exosome; mRNA stability; PM-Sc175
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Funding
- NCI NIH HHS [CA80062] Funding Source: Medline
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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. Immuno-depletion using antibodies specific for the exosomal protein PM-Sc175 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-Sc175 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.
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