Artículo
Human prefoldin modulates co-transcriptional pre-mRNA splicing
Autor/es | Payán Bravo, Laura
Fontalva Ostio, Sara Peñate Salas, Xenia Cases, Ildefonso Guerrero Martínez, José A. Pareja Sánchez, Yerma Odriozola Gil, Yosu Lara, Esther Jimeno González, Silvia Suñé Negre, Carlos María Muñoz Centeno, María de la Cruz Reyes, José C. Chávez de Diego, Sebastián |
Departamento | Universidad de Sevilla. Departamento de Genética |
Fecha de publicación | 2021 |
Fecha de depósito | 2021-07-16 |
Publicado en |
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Premios | Premio Anual Publicación Científica Destacada de la US. Facultad de Biología |
Resumen | Prefoldin is a heterohexameric complex conserved from archaea to humans that plays a cochaperone role during the co-translational folding of actin and tubulin monomers. Additional functions of prefoldin have been described, ... Prefoldin is a heterohexameric complex conserved from archaea to humans that plays a cochaperone role during the co-translational folding of actin and tubulin monomers. Additional functions of prefoldin have been described, including a positive contribution to transcription elongation and chromatin dynamics in yeast. Here we show that prefoldin perturbations provoked transcriptional alterations across the human genome. Severe pre-mRNA splicing defects were also detected, particularly after serum stimulation. We found impairment of co-transcriptional splicing during transcription elongation, which explains why the induction of long genes with a high number of introns was affected the most. We detected genome-wide prefoldin binding to transcribed genes and found that it correlated with the negative impact of prefoldin depletion on gene expression. Lack of prefoldin caused global decrease in Ser2 and Ser5 phosphorylation of the RNA polymerase II carboxy-terminal domain. It also reduced the recruitment of the CTD kinase CDK9 to transcribed genes, and the association of splicing factors PRP19 and U2AF65 to chromatin, which is known to depend on CTD phosphorylation. Altogether the reported results indicate that human prefoldin is able to act locally on the genome to modulate gene expression by influencing phosphorylation of elongating RNA polymerase II, and thereby regulating co-transcriptional splicing. |
Identificador del proyecto | BFU2016-77728-C3-1-P
BFU2017-85420-R P12- BIO1938MO BIO271 US-1256285 BIO321 |
Cita | Payán Bravo, L., Fontalva Ostio, S., Peñate Salas, X., Cases, I., Guerrero Martínez, J.A., Pareja Sánchez, Y.,...,Chávez de Diego, S. (2021). Human prefoldin modulates co-transcriptional pre-mRNA splicing. Nucleic Acids Research, 49 (11), 6267-6280. |
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