p38MAPK/MK2-mediated phosphorylation of RBM7 regulates the human nuclear exosome targeting complex.

Christopher Tiedje, Michal Lubas, Mohammad Tehrani, Manoj B Menon, Natalia Ronkina, Simon Rousseau, Philip Cohen, Alexey Kotlyarov, Matthias Gaestel

RNA (New York, N.Y.) 2015 Feb

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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. © 2015 Tiedje et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Citation

Christopher Tiedje, Michal Lubas, Mohammad Tehrani, Manoj B Menon, Natalia Ronkina, Simon Rousseau, Philip Cohen, Alexey Kotlyarov, Matthias Gaestel. p38MAPK/MK2-mediated phosphorylation of RBM7 regulates the human nuclear exosome targeting complex. RNA (New York, N.Y.). 2015 Feb;21(2):262-78