Human prefoldin modulates co-transcriptional pre-mRNA splicing

Abstract Prefoldin is a heterohexameric complex conserved from archaea to humans that plays cochaperone role during the co-translational folding of actin and tubulin monomers. Additional functions prefoldin have been described, including positive contribution transcription elongation chromatin dynamics in yeast. Here we show perturbations provoked transcriptional alterations across human genome. Severe pre-mRNA splicing defects were also detected, particularly after serum stimulation. We found impairment co-transcriptional elongation, which explains why induction long genes with high number introns was affected most. detected genome-wide binding transcribed it correlated negative impact depletion on gene expression. Lack caused global decrease Ser2 Ser5 phosphorylation RNA polymerase II carboxy-terminal domain. It reduced recruitment CTD kinase CDK9 genes, association factors PRP19 U2AF65 chromatin, known depend phosphorylation. Altogether reported results indicate able act locally genome modulate expression by influencing elongating II, thereby regulating splicing.