Anales RANF

P.46 AGE-RELATED NUCLEAR TRANSLOCATION OF P2X6 SUBUNIT MODIFIES SPLICING ACTIVITY INTERACTING WITH SPLICING FACTOR 3A1 Juan Ignacio Díaz-Hernández, Álvaro Sebastián-Serrano, Rosa Gomez-Villafuertes, Miguel Díaz-Hernández, María Teresa Miras-Portugal. Complutense University of Madrid, Madrid, Spain P2X6 subunit expression and immunoreactivity is observed throughout the central nervous system, especially in hippocampus and cerebellum. The ability if this subunit to form homomeric receptors is very inefficient, but its presence associated with P2X2 and P2X4 subunits is well documented. The abundance of mRNA and protein expression of P2X6 in hippocampus is relatively high in neuronal bodies of CA1, CA2, CA3 regions and dentate gyrus. 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. Noticeable, a similar nuclear location of P2X6 subunits was observed in ependymal spinal cord-derived stem/progenitor cells from adult rats. This nuclear location is favored by its anchorage to endoplasmic reticulum through its N-terminal domain, and interestingly, we found that the extracellular domain of P2X6 subunit is responsible for its nuclear and perinuclear location. Nuclear P2X6 subunit presents a speckled distribution pattern and is retained by interaction with the nuclear envelope protein spectrin α 2. 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. Thus, the negative modulation that nuclear accumulation of the P2X6 subunit elicits on splicing activity, could explain, at least in part, the events associated with cellular reprogramming of neuronal consolidation. References : • Díaz-Hernández JI, Sebastián-Serrano Á, Gómez-Villafuertes R, Díaz-Hernández M, Miras-Portugal MT. (2015) Age-related nuclear translocation of P2X6 subunit modifies splicing activity interacting with splicing factor 3A1. PLoS One 10(4):e0123121. • Purinergic Receptors in Spinal Cord-Derived Ependymal Stem/Progenitor Cells and Their Potential Role in Cell-Based Therapy for Spinal Cord Injury. (2015) Gómez-Villafuertes R, Rodríguez-Jiménez FJ, Alastrue-Agudo A, Stojkovic M, Miras-Portugal MT, Moreno-Manzano V. Cell Transplant 24(8):1493-509.