Portal de Periódicos da CAPES

AU Binding Proteins Recruit the Exosome to Degrade ARE-Containing mRNAs

2001; Cell Press; Volume: 107; Issue: 4 Linguagem: Inglês

10.1016/s0092-8674(01)00578-5

1097-4172

Ching‐Yi Chen, Roberto Gherzi, Shao‐En Ong, Edward K. L. Chan, Reinout Raijmakers, Ger J.M. Pruijn, Georg Stoecklin, Christoph Moroni, Matthias Mann, Michael Karin,

RNA Interference and Gene Delivery

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.