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

@article{Chen2001AUBP,
  title={AU Binding Proteins Recruit the Exosome to Degrade ARE-Containing mRNAs},
  author={Ching‐Yi Chen and Roberto Gherzi and Shao-En Ong and Edward K. L. Chan and Reinout Raijmakers and Ger J. M. Pruijn and Georg Stoecklin and Christoph Moroni and Matthias Mann and Michael Karin},
  journal={Cell},
  year={2001},
  volume={107},
  pages={451-464}
}
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… 
A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery.
TLDR
It is demonstrated that KSRP, a KH domain-containing ARE-BP, is an essential factor for ARE-directed mRNA decay, which promotes rapid mRNA decay by recruiting degradation machinery to ARE-containing mRNAs.
Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAU.
TLDR
This work has identified RHAU, a putative DExH RNA helicase that was isolated in association with the ARE of urokinase plasminogen activator mRNA (ARE(uPA) and physically interacts with the deadenylase PARN and the human exosome and enhances thedeadenylation and decay of ARE( uPA)-mRNAs.
A role for the exosome in the in vivo degradation of unstable mRNAs.
TLDR
It is concluded that the exosome is required for the initiation of rapid degradation of unstable mRNAs in trypanosomes.
Localization of AU-rich Element-containing mRNA in Cytoplasmic Granules Containing Exosome Subunits*
Eukaryotic mRNAs can be degraded in either decapping/5′-to-3′ or 3′-to-5′ direction after deadenylation. In yeast and mammalian cells, decay factors involved in the 5′-to-3′ decay pathway are
In Vitro Characterization of the Activity of the Mammalian RNA Exosome on mRNAs in Ribosomal Translation Complexes.
TLDR
Protocols for in vitro reconstitution of ribosomal 80S elongation complexes on cap-labeled mRNAs and for assaying exosomal degradation of m RNAs in such complexes depending on the presence of GTPBP1 are described.
Tethering KSRP, a Decay-Promoting AU-Rich Element-Binding Protein, to mRNAs Elicits mRNA Decay
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By targeting the Rev response element of human immunodeficiency virus type 1 by using Rev-KSRP fusion protein, the results provide a foundation for the development of novel therapeutic strategies to inhibit specific gene expression in patients with acquired or hereditary diseases.
Multiple functions of tristetraprolin/TIS11 RNA-binding proteins in the regulation of mRNA biogenesis and degradation
TLDR
This review gathers the present knowledge on the functions of this family of RNA-binding proteins, including their role in AU-rich element-mediated mRNA decay and focuses on recent advances that support the concept of their broader involvement in distinct steps of mRNA biogenesis and degradation.
Dis3- and exosome subunit-responsive 3' mRNA instability elements.
TLDR
These findings imply a potentially novel mechanism of mRNA turnover that involves direct Dis3 and other exosome subunit recruitment to and/or regulation on mRNA substrates.
Highly Selective Actions of HuR in Antagonizing AU-Rich Element-Mediated mRNA Destabilization
TLDR
The data suggest that the ARE-binding specificity of HuR in vivo is modulated to interact only with and thus regulate specific AREs in a cell type- and physiological state-dependent manner.
Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors.
TLDR
This review highlights recent advances that have illuminated roles for the RNA exosome and its cofactors in specific biological pathways, alongside studies that attempted to dissect these activities through structural and biochemical characterization of nuclear and cytoplasmic RNAExosome complexes.
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