RNA metabolism is altered following DNA damage, but the underlying mechanisms are not well understood. Through a 14-3-3 interaction screen for DNA damage-induced protein interactions in human cells, we identified protein complexes connected to RNA biology. These include the nuclear exosome targeting (NEXT) complex that regulates turnover of noncoding RNAs termed promoter upstream transcripts (PROMPTs). We show that the NEXT subunit RBM7 is phosphorylated upon DNA damage by the MAPKAPK2 kinase and establish that this mediates 14-3-3 binding and decreases PROMPT binding. These findings and our observation that cells lacking RBM7 display DNA damage hypersensitivity link PROMPT turnover to the DNA damage response.

The Gurdon Institute Department of Biochemistry University of Cambridge Cambridge CB2 1QN United Kingdom; Genome Integrity Unit Danish Cancer Society Research Centre 2100 Copenhagen Denmark;

The Gurdon Institute Department of Biochemistry University of Cambridge Cambridge CB2 1QN United Kingdom; The Wellcome Trust Sanger Institute Hinxton Cambridge CB10 1SA United Kingdom

The Novo Nordisk Foundation Center for Protein Research Faculty of Health and Medical Sciences University of Copenhagen 2200 Copenhagen Denmark;

The Novo Nordisk Foundation Center for Protein Research Faculty of Health and Medical Sciences University of Copenhagen 2200 Copenhagen Denmark; Institute of Molecular and Translational Medicine Palacky University 77900 Olomouc Czech Republic;

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