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

Devi Mukherjee, Min Gao, J. Patrick O'Connor, Reinout Raijmakers, Ger Pruijn, Carol S. Lutz, Jeffrey Wilusz

Research output: Contribution to journalArticlepeer-review

310 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)165-174
Number of pages10
JournalEMBO Journal
Issue number1-2
StatePublished - Jan 15 2002

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


  • AU-rich elements
  • Exosome
  • PM-Sc175
  • mRNA stability


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