RT Journal Article T1 Age-Related Nuclear Translocation of P2X6 Subunit Modifies Splicing Activity Interacting with Splicing Factor 3A1 A1 Díaz-Hernández, Juan Ignacio A1 Sebastián Serrano, Álvaro A1 Gómez Villafuertes, María Rosa A1 Díaz Hernández, Miguel A1 Miras Portugal, María Teresa A2 Barbara Bardoni, AB P2X receptors are ligand-gated ion channels sensitive to extracellular nucleotides formed by the assembling of three equal or different P2X subunits. In this work we report, for the first time, the accumulation of the P2X6 subunit inside the nucleus of hippocampal neurons in an age-dependent way. This location is favored by its anchorage to endoplasmic reticulum through its N-terminal domain. The extracellular domain of P2X6 subunit is the key to reach the nucleus, where it presents a speckled distribution pattern and is retained by interaction with the nuclear envelope protein spectrin α2. The in vivo results showed that, once inside the nucleus, P2X6 subunit interacts with the splicing factor 3A1, which ultimately results in a reduction of the mRNA splicing activity. Our data provide new insights into post-transcriptional regulation of mRNA splicing, describing a novel mechanism that could explain why this process is sensitive to changes that occur with age. PB PLOS SN 1932-6203 YR 2015 FD 2015 LK https://hdl.handle.net/20.500.14352/96219 UL https://hdl.handle.net/20.500.14352/96219 LA eng NO Díaz-Hernández JI, Sebastián-Serrano Á, Gómez-Villafuertes R, Díaz-Hernández M, Miras-Portugal MT. Age-related nuclear translocation of P2X6 subunit modifies splicing activity interacting with splicing factor 3A1. PLoS One. 2015 Apr 13;10(4):e0123121. doi: 10.1371/journal.pone.0123121. PMID: 25874565; PMCID: PMC4395284. DS Docta Complutense RD 9 abr 2025