This work was supported by the Plan Nacional de I+D+I [2013‐2016/FEDER PI15/00892 to M.F.F. and A.F.F., 2008‐2011/FEDER CP11/00131 to A.F.F.]; the ISCIII‐Subdirección General de Evaluación y Fomento de la Investigación [Miguel Servet contract CP11/00131 to A.F.F.]; Instituto Universitario de Oncología del Principado de Asturias (IUOPA) to [G.F.B.]; Fundación Ramón Areces to [M.F.F.]; and the Asturias Regional Government [GRUPIN14‐052 to M.F.F.]. R.F.P. is supported by the Retención de Jóvenes Talentos Fellowship from the Obra Social Cajastur‐Liberbank. J.R.T. is supported by the Ministry of Economy and Competitiveness Through a Juan de la Cierva Postdoctoral Fellowship [FJCI‐2015‐26965]. The IUOPA is supported by the Obra Social Cajastur‐Liberbank, Spain.
The Asturias Government (PCTI) co-funding 2018-2022/FEDER (IDI/2018/146 to M.F.F.), the Fundación General CSIC (0348_CIE_6_E to M.F.F.), the Health Institute Carlos III (Plan Nacional de I+D+I) co-funding FEDER (PI18/01527 to M.F.F and A.F.F.), the MINECO (DEP2015-69980-P to B.F.G.). R.G.U. is supported by the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER). J.R.T. is supported by a Juan de la Cierva fellowship from the Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/ 501100011033 (IJC2018-036825-I) (.) ; Urdinguio, RG; Tejedor, JR; Fernandez-Sanjurjo, M; Perez, RF; Penarroya, A; Ferrero, C; Codina-Martinez, H; Diez-Planelles, C; Pinto-Hernandez, P; Castilla-Silgado, J; Coto-Vilcapoma, A; Diez-Robles, S; Blanco-Agudin, N; Tomas-Zapico, C; Iglesias-Gutierrez, E; Fernandez-Garcia, B; Fernandez, AF; Fraga, MF
Plan Nacional de I+D+I co-funding FEDER [PI15/00892 and PI18/01527 to M.F.F. and A.F.F.; PI16/01318 and PI14/01244 to C.L.]; ISCIII-Subdireccion General de Evaluación y Fomento de la Investigación, and Plan ´ Nacional de I+D+I 2008–2011/FEDER [CP11/00131 to A.F.F.]; IUOPA (to G.F.B. and M.I.S.); Fundación Científica de la AECC (to R.G.U.); Ministry of Economy and Competitiveness Juan de la Cierva postdoctoral fellowships [FJCI-2015-26965 to J.R.T., IJCI-2015- 23316 to V.L.]; Fundación Ramón Areces (to M.F.F); ´ FICYT (to E.G.T., M.G.G., A.C.); Asturias Regional Government [GRUPIN14-052 to M.F.F.]; Gobierno del Principado de Asturias, PCTI-Plan de Ciencia, Tecnología e Innovación co-funding Fondos FEDER (grant number IDI/2018/146 to M.F.F. and IDI/2018/144 to C.L.); Spanish Ministry of Economy and Competitiveness [SAF-SAF2013-43065 to P.M.]; Asociación Española Contra el Cáncer [AECC-CI-2015]; FERO Foundation, and the ISCIII [PI14-01191 to C.B.]; P.M. acknowledges financial support from The Obra Social La Caixa Fundación Josep Carreras and The Generalitat de Catalunya (SGR330). P.M. an investigator from the Spanish Cell Therapy cooperative network (TERCEL). The IUOPA is supported by the Obra Social Liberbank-Cajastur, Spain. Funding for open access charge: Plan Nacional de I+D+I co-funding FEDER [PI18/01527]. ; Urdinguio, R.G., Lopez, V., Bayón, G.F., Diaz De La Guardia, R., Sierra, M.I., García-Toraño, E., Perez, R.F., García, M.G., Carella, A., Pruneda, P.C., Prieto, C., Dmitrijeva, M., Santamarina, P., Belmonte, T., Mangas, C., Diaconu, E., Ferrero, C., Tejedor, J.R., Fernandez-Morera, J.L., Bravo, C., Bueno, C., Sanjuan-Pla, A., Rodriguez, R.M., Suarez-Alvarez, B., López-Larrea, C., Bernal, T., Colado, E., Balbín, M., García-Suarez, O., Chiara, M.D., Sáenz-De-Santa-María, I., Rodríguez, F., Pando-Sandoval, A., Rodrigo, L., Santos, L., Salas, A., Vallejo-Díaz, J., C Carrera, A., Rico, D., Hernández-López, I., Vayá, A., Ricart, J.M., Seto, E., Sima-Teruel, N., Vaquero, A., Valledor, L., Cañal, M.J., Pisano, D., ...
Alternative splicing is a prevalent mechanism of gene regulation that is modulated in response to a wide range of extracellular stimuli. Stress-activated protein kinases (SAPKs) play a key role in controlling several steps of mRNA biogenesis. Here, we show that osmostress has an impact on the regulation of alternative splicing (AS), which is partly mediated through the action of p38 SAPK. Splicing network analysis revealed a functional connection between p38 and the spliceosome component SKIIP, whose depletion abolished a significant fraction of p38-mediated AS changes. Importantly, p38 interacted with and directly phosphorylated SKIIP, thereby altering its activity. SKIIP phosphorylation regulated AS of GADD45α, the upstream activator of the p38 pathway, uncovering a negative feedback loop involving AS regulation. Our data reveal mechanisms and targets of SAPK function in stress adaptation through the regulation of AS. ; This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (BFU2015-64437-P and FEDER, PGC2018-094136-B-I00 and FEDER, BFU2014-52125-REDT, and BFU2014-51672-REDC to F.P.; BFU2017-85152-P and FEDER to E.d.N.; BFU2014-005153 to J.V.), the Catalan Government (2017 SGR 799), the European Research Council (AdvG 670146 to J.V.), the Fundación Botín and the Banco Santander through its Santander Universities Global Division (to F.P. and J.V.), the Unidad de Excelencia Maria de Maeztu (MDM-2014-0370), and the Centre of Excellence Severo Ochoa. F.P. is a recipient of an ICREA Acadèmia (Generalitat de Catalunya).
This work was supported by the Spanish Association Against Cancer (PROYE18061 FERN to M.F.F.), the Asturias Government (PCTI) cofunding 2018- 2022/FEDER (IDI/2018/146 to M.F.F.), Fundación General CSIC (0348_CIE_6_E to M.F.F.), and the Health Institute Carlos III (Plan Nacional de I þ DþI) cofunding FEDER (PI15/00892 and PI18/01527 to M.F.F and A.F.F.). They also acknowledge support from the Ramón Areces Foundation (CIVP18A3891 to P.J.F.M.), the AECC (SIRTBIO to P.J.F.M.), the MICINN (SAF2017-85766-R to P.J.F.M.), a Ramón y Cajal fellowship (MICINN, RYC-2017-22335 to P.J.F.M.), and the European Commission ATTRACT project (777222 to A.P.C.). J.R.T. is supported by a Juan de la Cierva fellowship from the Spanish Ministry of Science and Innovation (FJCI-2015-26965). R.F.P. and P.S.O. are supported by the Severo Ochoa program (BP17-114 and BP17-165, respectively). R.G.U. is supported by the Centro de Investigación Biomédica en Red de Enfermedades Raras (Health Institute Carlos III). L.V. was supported by the UAB Predoctoral training programme (PIF predoctoral fellowships). They also acknowledge support from the IMDEA Food Institute and IUOPA-ISPA-FINBA (the IUOPA is supported by the Obra Social Cajastur-Liberbank, Spain).
This work has been financially supported by the Plan Nacional de I+D+I 2013-2016/FEDER (PI15/00892 to M.F.F. and A.F.F.), the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación (Miguel Servet contract CP11/00131 to A.F.F.); the Asturias Regional Government (GRUPIN14-052 to M.F.F.); FICYT (A.C. and M.G.); the Ministry of Economy and Competitiveness of Spain (J.R.T., Juan de la Cierva fellowship FJCI-2015-26965, V.L., Juan de la Cierva fellowship IJCI-2015-23316); Fundación Científica de la AECC (to R.G.U.); FINBA-ISPA (R.F.P.); IUOPA (G.F.B. and C.M.) and Fundación Ramón Areces (M.F.F.). A.F.F. is also financially supported by the Ministry of Economy and Competitiveness of Spain, the European Regional Development Fund (FEDER) and the Programa Retos de la Sociedad (RTC-2015-3393-1). The IUOPA is supported by the Obra Social Cajastur-Liberbank, Spain.