p38-MK2 signaling axis regulates RNA metabolism after UV light-induced DNA damage

Ultraviolet (UV) light radiation induces the formation of bulky photoproducts in the DNA that interfere with replication and transcription. Recent studies showed that exposure of human cells to UV light globally affects transcription and alternative splicing, however, the signaling pathways and mechanisms that link UV light-induced DNA damage to RNA metabolism regulation remain poorly understood. Here, we provide a systems view on protein phosphorylation patterns induced by UV light, and uncover the dependencies of phosphorylation events on the canonical DNA damage signaling mediated by ATM/ATR or p38 MAP kinase pathway. We identify RNA binding proteins as primary targets and 14-3-3 family as direct readers of p38-MK2-dependent phosphorylation induced by UV light. Moreover, we show that MK2 phosphorylates the RNA binding subunit of the NELF complex NELFE on S115. NELFE phosphorylation promotes the recruitment of 14-3-3 and rapid dissociation of the NELF complex from chromatin that is accompanied with an increase in transcriptional elongation.