AU binding proteins recruit the exosome to degrade ARE-containing mRNAs

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

Research output: Contribution to journalArticle

684 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)451-464
Number of pages14
JournalCell
Volume107
Issue number4
DOIs
Publication statusPublished - Nov 16 2001

Fingerprint

AU Rich Elements
Exosomes
Carrier Proteins
Messenger RNA
RNA Stability
RNA
Degradation
Yeast
Yeasts
Poly A
3' Untranslated Regions
Mass spectrometry
Mass Spectrometry
Chemical analysis

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Chen, C. Y., Gherzi, R., Ong, S. E., Chan, E. L., Raijmakers, R., Pruijn, G. J. M., ... Karin, M. (2001). AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell, 107(4), 451-464. https://doi.org/10.1016/S0092-8674(01)00578-5

AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. / Chen, Ching Yi; Gherzi, Roberto; Ong, Shao En; Chan, Edward L.; Raijmakers, Reinout; Pruijn, Ger J M; Stoecklin, Georg; Moroni, Christoph; Mann, Matthias; Karin, Michael.

In: Cell, Vol. 107, No. 4, 16.11.2001, p. 451-464.

Research output: Contribution to journalArticle

Chen, CY, Gherzi, R, Ong, SE, Chan, EL, Raijmakers, R, Pruijn, GJM, Stoecklin, G, Moroni, C, Mann, M & Karin, M 2001, 'AU binding proteins recruit the exosome to degrade ARE-containing mRNAs', Cell, vol. 107, no. 4, pp. 451-464. https://doi.org/10.1016/S0092-8674(01)00578-5
Chen CY, Gherzi R, Ong SE, Chan EL, Raijmakers R, Pruijn GJM et al. AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell. 2001 Nov 16;107(4):451-464. https://doi.org/10.1016/S0092-8674(01)00578-5
Chen, Ching Yi ; Gherzi, Roberto ; Ong, Shao En ; Chan, Edward L. ; Raijmakers, Reinout ; Pruijn, Ger J M ; Stoecklin, Georg ; Moroni, Christoph ; Mann, Matthias ; Karin, Michael. / AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. In: Cell. 2001 ; Vol. 107, No. 4. pp. 451-464.
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