K63-Ubiquitylation and TRAF6 Pathways Regulate Mammalian P-Body Formation and mRNA Decapping

Ulas Tenekeci, Michael Poppe, Knut Beuerlein, Christin Buro, Helmut Müller, Hendrik Weiser, Daniela Kettner-Buhrow, Katharina Porada, Doris Newel, Ming Xu, Zhijian J. Chen, Julia Busch, M. Lienhard Schmitz, Michael Kracht

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Signals and posttranslational modifications regulating the decapping step in mRNA degradation pathways are poorly defined. In this study we reveal the importance of K63-linked ubiquitylation for the assembly of decapping factors, P-body formation, and constitutive decay of instable mRNAs encoding mediators of inflammation by various experimental approaches. K63-branched ubiquitin chains also regulate IL-1-inducible phosphorylation of the P-body component DCP1a. The E3 ligase TRAF6 binds to DCP1a and indirectly regulates DCP1a phosphorylation, expression of decapping factors, and gene-specific mRNA decay. Mutation of six C-terminal lysines of DCP1a suppresses decapping activity and impairs the interaction with the mRNA decay factors DCP2, EDC4, and XRN1, but not EDC3, thus remodeling P-body architecture. The usage of ubiquitin chains for the proper assembly and function of the decay-competent mammalian decapping complex suggests an additional layer of control to allow a coordinated function of decapping activities and mRNA metabolism in higher eukaryotes.

Original languageEnglish (US)
Pages (from-to)943-957
Number of pages15
JournalMolecular cell
Volume62
Issue number6
DOIs
StatePublished - Jun 16 2016

Keywords

  • DCP1a
  • IL-1
  • K63R ubiquitin
  • P-body
  • TRAF6
  • Ubiquitin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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