Histone H3K36 methylation regulates pre-mRNA splicing in Saccharomyces cerevisiae

RNA Biology
Matthew R SorensonTracy L Kress

Abstract

Co-transcriptional splicing takes place in the context of a highly dynamic chromatin architecture, yet the role of chromatin restructuring in coordinating transcription with RNA splicing has not been fully resolved. To further define the contribution of histone modifications to pre-mRNA splicing in Saccharomyces cerevisiae, we probed a library of histone point mutants using a reporter to monitor pre-mRNA splicing. We found that mutation of H3 lysine 36 (H3K36) - a residue methylated by Set2 during transcription elongation - exhibited phenotypes similar to those of pre-mRNA splicing mutants. We identified genetic interactions between genes encoding RNA splicing factors and genes encoding the H3K36 methyltransferase Set2 and the demethylase Jhd1 as well as point mutations of H3K36 that block methylation. Consistent with the genetic interactions, deletion of SET2, mutations modifying the catalytic activity of Set2 or H3K36 point mutations significantly altered expression of our reporter and reduced splicing of endogenous introns. These effects were dependent on the association of Set2 with RNA polymerase II and H3K36 dimethylation. Additionally, we found that deletion of SET2 reduces the association of the U2 and U5 snRNPs with ch...Continue Reading

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Citations

Apr 8, 2017·Cellular and Molecular Life Sciences : CMLS·Stephen L McDaniel, Brian D Strahl
Jan 10, 2018·Proceedings of the National Academy of Sciences of the United States of America·Catherine BélangerNicolas Pilon
Jul 27, 2018·Epigenetics : Official Journal of the DNA Methylation Society·Brianna J KleinTatiana G Kutateladze
May 10, 2017·Molecular and Cellular Biology·Camille SayouDavid Tollervey
Jun 5, 2020·Cold Spring Harbor Symposia on Quantitative Biology·Tucker J Carrocci, Karla M Neugebauer
Mar 5, 2020·Wiley Interdisciplinary Reviews. RNA·Michael TellierShona Murphy
Feb 23, 2019·Nucleic Acids Research·Rajaraman GopalakrishnanFred Winston
Apr 26, 2019·Molecular Genetics and Genomics : MGG·Amy TsurumiWillis X Li
Apr 28, 2017·Genes & Development·Lauren T NevesTracy L Johnson
Jul 6, 2021·The Journal of Biological Chemistry·Ryan J Separovich, Marc R Wilkins

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Methods Mentioned

BETA
immunoprecipitations
acetylation
ubiquitination
flow cytometry
SGA
immunoprecipitation
ChIP
PCR
ChIPs

Software Mentioned

Cluster
TreeView

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