AU binding proteins recruit the exosome to degrade ARE-containing mRNAs.
Inherently unstable mammalian mRNAs contain AU-rich elements (AREs) within their 3' untranslated regions. Although found 15 years ago, the mechanism by which AREs dictate rapid mRNA decay is not clear. In yeast, 3'-to-5' mRNA degradation is mediated by the exosome, a multisubunit particle. We have purified and characterized the human exosome by mass spectrometry and found its composition to be similar to its yeast counterpart. Using a cell-free RNA decay system, we demonstrate that the mammalian exosome is required for rapid degradation of ARE-containing RNAs but not for poly(A) shortening. The mammalian exosome does not recognize ARE-containing RNAs on its own. ARE recognition requires certain ARE binding proteins that can interact with the exosome and recruit it to unstable RNAs, thereby promoting their rapid degradation.
Chen
C Y
CY
Department of Pharmacology, Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, La Jolla, CA 92093, USA.
Gherzi
R
R
Ong
S E
SE
Chan
E L
EL
Raijmakers
R
R
Pruijn
G J
GJ
Stoecklin
G
G
Moroni
C
C
Mann
M
M
Karin
M
M
D020413:3' Untranslated Regions / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D002474:Cell-Free System; D020868:Gene Silencing / Q000502:physiology*; D016762:Genes, fos; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism; D008322:Mammals / Q000235:genetics; D008969:Molecular Sequence Data; D011061:Poly A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013942:Thymine Nucleotides / Q000494:pharmacology; D015534:Trans-Activators
D020413:3' Untranslated Regions; D007376:Interleukin-2; C105789:KHSRP protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D013942:Thymine Nucleotides; D015534:Trans-Activators; D011061:Poly A; C024157:thymidine 5'-triphosphate