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 b y 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 p urified and characterized the human exosome by mass spectrometry and found its composition to be similar to its yeast counterpart. Using a cell-free R NA decay system, we demonstrate that the mammalian exosome is required for rapid degradation of ARE-containing RNAs but not for poly(A) shortening. Th e mammalian exosome does not recognize ARE-containing RNAs on its own. ARE recognition requires certain ARE binding proteins that can interact with th e exosome and recruit it to unstable RNAs, thereby promoting their rapid de gradation.