Salas-Armenteros, IreneBarroso, Sonia IRondón, Ana GPérez, MónicaAndújar, EloisaLuna, RosaAguilera, Andrés2023-01-252023-01-252019http://hdl.handle.net/10668/14374THO/TREX is a conserved complex with a role in messenger ribonucleoprotein biogenesis that links gene expression and genome instability. Here, we show that human THO interacts with MFAP1 (microfibrillar-associated protein 1), a spliceosome-associated factor. Interestingly, MFAP1 depletion impairs cell proliferation and genome integrity, increasing γH2AX foci and DNA breaks. This phenotype is not dependent on either transcription or RNA-DNA hybrids. Mutations in the yeast orthologous gene SPP381 cause similar transcription-independent genome instability, supporting a conserved role. MFAP1 depletion has a wide effect on splicing and gene expression in human cells, determined by transcriptome analyses. MFAP1 depletion affects a number of DNA damage response (DDR) genes, which supports an indirect role of MFAP1 on genome integrity. Our work defines a functional interaction between THO and RNA processing and argues that splicing factors may contribute to genome integrity indirectly by regulating the expression of DDR genes rather than by a direct role.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/MFAP1/SPP381THO complexalternative splicinggenome instabilityAlternative SplicingCell CycleCell ProliferationContractile ProteinsDNA-Binding ProteinsExtracellular Matrix ProteinsGene Expression RegulationGenome, HumanGenomic InstabilityHEK293 CellsHeLa CellsHumansR-Loop StructuresRNA Processing, Post-TranscriptionalRNA Splicing FactorsRNA-Binding ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSpliceosomesresearch article31390568open access10.1016/j.celrep.2019.07.0102211-1247PMC6693559http://www.cell.com/article/S2211124719309003/pdf