RT Journal Article
SR Electronic
T1 The Splicing Factor XAB2 interacts with ERCC1-XPF and XPG for RNA-loop processing during mammalian development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.20.211441
DO 10.1101/2020.07.20.211441
A1 Evi Goulielmaki
A1 Maria Tsekrekou
A1 Nikos Batsiotos
A1 Mariana Ascensão-Ferreira
A1 Eleftheria Ledaki
A1 Kalliopi Stratigi
A1 Georgia Chatzinikolaou
A1 Pantelis Topalis
A1 Theodore Kosteas
A1 Janine Altmüller
A1 Jeroen A. Demmers
A1 Nuno L. Barbosa-Morais
A1 George A. Garinis
YR 2020
UL http://biorxiv.org/content/early/2020/07/21/2020.07.20.211441.abstract
AB RNA splicing, transcription and the DNA damage response are intriguingly linked in mammals but the underlying mechanisms remain poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the splicing factor XAB2 interacts with the core spliceosome and that it binds to spliceosomal U4 and U6 snRNAs and pre-mRNAs in developing livers. XAB2 depletion leads to aberrant intron retention, R-loop formation and DNA damage in cells. Studies in illudin S-treated cells and Csbm/m developing livers reveal that transcription-blocking DNA lesions trigger the release of XAB2 from all RNA targets tested. Immunoprecipitation studies reveal that XAB2 interacts with ERCC1-XPF and XPG endonucleases outside nucleotide excision repair and that the trimeric protein complex binds RNA:DNA hybrids under conditions that favor the formation of R-loops. Thus, XAB2 functionally links the spliceosomal response to DNA damage with R-loop processing with important ramifications for mammalian development and transcription-coupled DNA repair disorders.Competing Interest StatementThe authors have declared no competing interest.