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

Area of Science:

• Molecular Biology
• RNA Biology
• Cell Signaling

Background:

• The nuclear exosome targeting complex (NEXT) facilitates the degradation of nuclear noncoding RNAs (ncRNAs) via the RNA exosome.
• Understanding the regulation of ncRNA stability is crucial for comprehending cellular responses to stress.

Purpose of the Study:

• To investigate the role of RBM7, an RNA-binding component of the NEXT complex, in regulating ncRNA stability.
• To elucidate the impact of p38(MAPK)/MK2 signaling on RBM7 function and ncRNA metabolism.

Main Methods:

• Phosphorylation site identification in RBM7.
• RNA-binding assays to assess RBM7-RNA interactions under different conditions.
• Analysis of promoter-upstream transcripts (PROMPTs) accumulation and stability.
• Assessment of RNA-polymerase II (RNAPII) occupation in PROMPT regions.

Main Results:

• RBM7 is phosphorylated by p38(MAPK)/MK2 at serine 136 (S136).
• Phosphorylation at S136 significantly reduces RBM7's RNA-binding capacity.
• Stress stimulation leads to p38(MAPK)/MK2-dependent accumulation of PROMPTs, which is inhibited by RBM7(S136A) overexpression.
• PROMPTs exhibit increased stability upon stress, without changes in RNAPII transcription levels.

Conclusions:

• Phosphorylation of RBM7 by the p38(MAPK)/MK2 pathway enhances nuclear ncRNA stability.
• This mechanism involves reduced RBM7 binding to ncRNAs, thereby preventing their targeting by the RNA exosome.
• The findings reveal a novel pathway for stress-dependent modulation of the noncoding transcriptome.