p38MAPK/MK2-mediated phosphorylation of RBM7 regulates the human nuclear exosome targeting complex
- RNA. 2015 Feb;21(2):262-78. doi: 10.1261/rna.048090.114.
- 1. Institute of Physiological Chemistry, Hannover Medical School, 30625 Hannover, Germany [email protected] [email protected].
- 2. Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark.
- 3. Institute of Physiological Chemistry, Hannover Medical School, 30625 Hannover, Germany.
- 4. MRC Phosphorylation und Ubiquitylation Unit (MRC-PPU), Dundee, Scotland DD1 5EH, United Kingdom.
The nuclear exosome targeting complex (NEXT) directs a major 3'-5' exonuclease, the RNA exosome, for degradation of nuclear noncoding (nc) RNAs. We identified the RNA-binding component of the NEXT complex, RBM7, as a substrate of p38(MAPK)/MK2-mediated phosphorylation at residue S136. As a result of this phosphorylation, RBM7 displays a strongly decreased RNA-binding capacity, while inhibition of p38(MAPK) or mutation of S136A in RBM7 increases its RNA association. Interestingly, promoter-upstream transcripts (PROMPTs), such as proRBM39, proEXT1, proDNAJB4, accumulated upon stress stimulation in a p38(MAPK)/MK2-dependent manner, a process inhibited by overexpression of RBM7(S136A). While there are no stress-dependent changes in RNA-polymerase II (RNAPII) occupation of PROMPT regions representing unchanged transcription, stability of PROMPTs is increased. Hence, we propose that phosphorylation of RBM7 by the p38(MAPK)/MK2 axis increases nuclear ncRNA stability by blocking their RBM7-binding and subsequent RNA exosome targeting to allow stress-dependent modulations of the noncoding transcriptome.