Montes, MartaCoiras, MayteBecerra, SorayaMoreno-Castro, CristinaMateos, ElenaMajuelos, JaraOliver, F JavierHernández-Munain, CristinaAlcamí, JoséSuñé, Carlos2018-12-192018-12-192015-10-13PLoS One. 2015 Oct 13;10(10):e01398121932-6203http://hdl.handle.net/20.500.12105/6910Here, we present evidence for a specific role of the splicing-related factor TCERG1 in regulating apoptosis in live cells by modulating the alternative splicing of the apoptotic genes Bcl-x and Fas. We show that TCERG1 modulates Bcl-x alternative splicing during apoptosis and its activity in Bcl-x alternative splicing correlates with the induction of apoptosis, as determined by assessing dead cells, sub-G1-phase cells, annexin-V binding, cell viability, and cleavage of caspase-3 and PARP-1. Furthermore, the effect of TCERG1 on apoptosis involved changes in mitochondrial membrane permeabilization. We also found that depletion of TCERG1 reduces the expression of the activated form of the pro-apoptotic mitochondrial membrane protein Bak, which remains inactive by heterodimerizing with Bcl-xL, preventing the initial step of cytochrome c release in Bak-mediated mitochondrial apoptosis. In addition, we provide evidence that TCERG1 also participates in the death receptor-mediated apoptosis pathway. Interestingly, TCERG1 also modulates Fas/CD95 alternative splicing. We propose that TCERG1 sensitizes a cell to apoptotic agents, thus promoting apoptosis by regulating the alternative splicing of both the Bcl-x and Fas/CD95 genes. Our findings may provide a new link between the control of alternative splicing and the molecular events leading to apoptosis.engVoRhttp://creativecommons.org/licenses/by/4.0/Alternative SplicingApoptosisCaspase 3Cytochromes cHEK293 CellsHeLa CellsHumansJurkat CellsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesTranscriptional Elongation Factorsbcl-2 Homologous Antagonist-Killer Proteinbcl-X Proteinfas ReceptorAtribución 4.0 Internacional264622361010e013981210.1371/journal.pone.01398121932-6203PloS oneopen access