p38MAPK/MK2-mediated phosphorylation of RBM7 regulates the human nuclear exosome targeting complex
- Christopher Tiedje1,
- Michal Lubas2,4,
- Mohammad Tehrani1,
- Manoj B. Menon1,
- Natalia Ronkina1,
- Simon Rousseau3,5,
- Philip Cohen3,
- Alexey Kotlyarov1 and
- Matthias Gaestel1
- 1Institute of Physiological Chemistry, Hannover Medical School, 30625 Hannover, Germany
- 2Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark
- 3MRC Phosphorylation und Ubiquitylation Unit (MRC-PPU), Dundee, Scotland DD1 5EH, United Kingdom
- Corresponding authors: Tiedje.Christopher{at}mh-hannover.de; Gaestel.Matthias{at}mh-hannover.de
Abstract
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 p38MAPK/MK2-mediated phosphorylation at residue S136. As a result of this phosphorylation, RBM7 displays a strongly decreased RNA-binding capacity, while inhibition of p38MAPK 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 p38MAPK/MK2-dependent manner, a process inhibited by overexpression of RBM7S136A. 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 p38MAPK/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.
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.048090.114.
- Received September 12, 2014.
- Accepted November 19, 2014.
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