Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
2.
Mol Cell ; 62(6): 943-957, 2016 06 16.
Article in English | MEDLINE | ID: mdl-27315556

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.


Subject(s)
Endoribonucleases/metabolism , Lysine/metabolism , RNA Caps/metabolism , RNA Stability , RNA, Messenger/metabolism , TNF Receptor-Associated Factor 6/metabolism , Trans-Activators/metabolism , Ubiquitination , Animals , Cell Line, Tumor , Endoribonucleases/genetics , Exoribonucleases/metabolism , HEK293 Cells , Humans , Interleukin-1alpha/pharmacology , Intracellular Signaling Peptides and Proteins , Mice , Microtubule-Associated Proteins/metabolism , Mutation , Phosphorylation , Protein Binding , Protein Interaction Domains and Motifs , Proteins/metabolism , RNA Caps/genetics , RNA Stability/drug effects , RNA, Messenger/genetics , Receptors, Interleukin-1/agonists , Receptors, Interleukin-1/genetics , Receptors, Interleukin-1/metabolism , TNF Receptor-Associated Factor 6/genetics , Time Factors , Trans-Activators/genetics , Transfection , Ubiquitination/drug effects
SELECTION OF CITATIONS
SEARCH DETAIL
...