Defective histone supply causes changes in RNA polymerase II elongation rate and cotranscriptional pre-mRNA splicing.

ABSTRACT: RNA polymerase II (RNAPII) transcription elongation is a highly regulated process that greatly influences mRNA levels as well as pre-mRNA splicing. Despite many studies in vitro, how chromatin modulates RNAPII elongation in vivo is still unclear. Here, we show that a decrease in the level of available canonical histones leads to more accessible chromatin with decreased levels of canonical histones and variants H2A.X and H2A.Z and increased levels of H3.3. With this altered chromatin structure, the RNAPII elongation rate increases, and the kinetics of pre-mRNA splicing is delayed with respect to RNAPII elongation. Consistent with the kinetic model of cotranscriptional splicing, the rapid RNAPII elongation induced by histone depletion promotes the skipping of variable exons in the CD44 gene.

SUBMITTER: Jimeno-Gonzalez S 

PROVIDER: S-EPMC4672771 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature