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 language | English (US) |
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Pages (from-to) | 943-957 |
Number of pages | 15 |
Journal | Molecular cell |
Volume | 62 |
Issue number | 6 |
DOIs | |
State | Published - Jun 16 2016 |
Keywords
- DCP1a
- IL-1
- K63R ubiquitin
- P-body
- TRAF6
- Ubiquitin
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology