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The splicing factor XAB2 interacts with ERCC1-XPF and XPG for R-loop processing

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Item Type:Letter
Title:The splicing factor XAB2 interacts with ERCC1-XPF and XPG for R-loop processing
Creators Name:Goulielmaki, E. and Tsekrekou, M. and Batsiotos, N. and Ascensão-Ferreira, M. and Ledaki, E. and Stratigi, K. and Chatzinikolaou, G. and Topalis, P. and Kosteas, T. and Altmüller, J. and Demmers, J.A. and Barbosa-Morais, N.L. and Garinis, G.A.
Abstract: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 Csb(m/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 transcription-coupled DNA repair disorders.
Keywords:Cell Line, Developmental Gene Expression Regulation, DNA Damage, DNA Repair, DNA-Binding Proteins, Endonucleases, Gene Knock-In Techniques, Gene Knockdown Techniques, Genetic Transcription, Liver, Mouse Embryonic Stem Cells, Nuclear Proteins, Polycyclic Sesquiterpenes, R-Loop Structures, Recombinant Proteins, RNA Precursors, RNA Splicing Factors, RNA-Seq, Small Nuclear RNA, Spliceosomes, Transcription Factors, Transgenic Mice, Animals, Mice
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:3153
Date:26 May 2021
Official Publication:https://doi.org/10.1038/s41467-021-23505-1
PubMed:View item in PubMed

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