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00925njm 22002777a 4500 dc Díaz-Hernández, Juan Ignacio author Sebastián Serrano, Álvaro author Gómez Villafuertes, María Rosa author Díaz Hernández, Miguel author Miras Portugal, María Teresa author 2015 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. 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. 1932-6203 10.1371/journal.pone.0123121 https://hdl.handle.net/20.500.14352/96219 https://doi.org/10.1371/journal.pone.0123121 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123121 Age-Related Nuclear Translocation of P2X6 Subunit Modifies Splicing Activity Interacting with Splicing Factor 3A1