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 journalArticle

10 Citations (Scopus)

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

Fingerprint

TNF Receptor-Associated Factor 6
Ubiquitination
RNA Stability
Messenger RNA
Ubiquitin
Phosphorylation
Inflammation Mediators
Ubiquitin-Protein Ligases
Post Translational Protein Processing
Eukaryota
Interleukin-1
Lysine
Mutation
Genes

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Tenekeci, U., Poppe, M., Beuerlein, K., Buro, C., Müller, H., Weiser, H., ... Kracht, M. (2016). K63-Ubiquitylation and TRAF6 Pathways Regulate Mammalian P-Body Formation and mRNA Decapping. Molecular Cell, 62(6), 943-957. https://doi.org/10.1016/j.molcel.2016.05.017

K63-Ubiquitylation and TRAF6 Pathways Regulate Mammalian P-Body Formation and mRNA Decapping. / Tenekeci, Ulas; Poppe, Michael; Beuerlein, Knut; Buro, Christin; Müller, Helmut; Weiser, Hendrik; Kettner-Buhrow, Daniela; Porada, Katharina; Newel, Doris; Xu, Ming; Chen, Zhijian J.; Busch, Julia; Schmitz, M. Lienhard; Kracht, Michael.

In: Molecular Cell, Vol. 62, No. 6, 16.06.2016, p. 943-957.

Research output: Contribution to journalArticle

Tenekeci, U, Poppe, M, Beuerlein, K, Buro, C, Müller, H, Weiser, H, Kettner-Buhrow, D, Porada, K, Newel, D, Xu, M, Chen, ZJ, Busch, J, Schmitz, ML & Kracht, M 2016, 'K63-Ubiquitylation and TRAF6 Pathways Regulate Mammalian P-Body Formation and mRNA Decapping', Molecular Cell, vol. 62, no. 6, pp. 943-957. https://doi.org/10.1016/j.molcel.2016.05.017
Tenekeci U, Poppe M, Beuerlein K, Buro C, Müller H, Weiser H et al. K63-Ubiquitylation and TRAF6 Pathways Regulate Mammalian P-Body Formation and mRNA Decapping. Molecular Cell. 2016 Jun 16;62(6):943-957. https://doi.org/10.1016/j.molcel.2016.05.017
Tenekeci, Ulas ; Poppe, Michael ; Beuerlein, Knut ; Buro, Christin ; Müller, Helmut ; Weiser, Hendrik ; Kettner-Buhrow, Daniela ; Porada, Katharina ; Newel, Doris ; Xu, Ming ; Chen, Zhijian J. ; Busch, Julia ; Schmitz, M. Lienhard ; Kracht, Michael. / K63-Ubiquitylation and TRAF6 Pathways Regulate Mammalian P-Body Formation and mRNA Decapping. In: Molecular Cell. 2016 ; Vol. 62, No. 6. pp. 943-957.
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