title: The mammalian exosome mediates the efficient degradation of mRNAs that contain AU-rich elements.
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.
authors.affiliation: Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Devi
authors.initials: D
authors.lastname: Mukherjee
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: J Patrick
authors.initials: JP
authors.lastname: O'Connor
authors.forename: Reinout
authors.initials: R
authors.lastname: Raijmakers
authors.forename: Ger
authors.initials: G
authors.lastname: Pruijn
authors.forename: Carol S
authors.initials: CS
authors.lastname: Lutz
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wilusz
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D003593:Cytoplasm / Q000378:metabolism; D043211:Exodeoxyribonuclease V; D005090:Exodeoxyribonucleases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005090:Exodeoxyribonucleases; D043211:Exodeoxyribonuclease V