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Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation rate.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE228240 | GEO | 2023/11/07

REPOSITORIES: GEO

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Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation rate [PRO-seq]

Project description:Histones shape chromatin structure and the epigenetic landscape. H1, the most diverse histone in the human genome, has 11 variants. Due to high structural similarity between the H1s, their unique functions in transferring information from the chromatin to mRNA processing machineries, have remained elusive. Here, we generated human cell lines lacking up to five H1 subtypes, allowing us to characterize the genomic binding profiles of six H1 variants. Most H1s bind to specific sites, and binding depends on multiple factors including GC content. The highly expressed H1.2 has a high affinity for exons, whereas H1.3 binds intronic sequences. Although H1s have a minor effect on global gene expression levels, they are major splicing regulators, especially of exon skipping and intron retention events, through their effects on the elongation rate of RNA polymerase II. Thus, H1 variants determine splicing fate by modulating the RNA polymerase II elongation rate.

2023-11-07 | GSE228793 | GEO

Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation rate [ChIP-seq]

2023-11-07 | GSE228239 | GEO

Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation rate [RNA-seq]

2023-11-07 | GSE228238 | GEO

Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation rate.

Project description:Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation rate.

| PRJNA949100 | ENA

Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation rate [ChIP-seq]

Project description:Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation rate [ChIP-seq]

| PRJNA949108 | ENA

Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation rate [PRO-seq]

Project description:Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation rate [PRO-seq]

| PRJNA951642 | ENA

Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation rate [RNA-seq]

Project description:Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation rate [RNA-seq]

| PRJNA949107 | ENA

Pre-mRNA splicing is facilitated by an optimal RNA polymerase II elongation rate.

Project description:Alternative splicing modulates expression of most human genes. The kinetic model of cotranscriptional splicing suggests that slow elongation expands and that fast elongation compresses the "window of opportunity" for recognition of upstream splice sites, thereby increasing or decreasing inclusion of alternative exons. We tested the model using RNA polymerase II mutants that change average elongation rates genome-wide. Slow and fast elongation affected constitutive and alternative splicing, frequently altering exon inclusion and intron retention in ways not predicted by the model. Cassette exons included by slow and excluded by fast elongation (type I) have weaker splice sites, shorter flanking introns, and distinct sequence motifs relative to "slow-excluded" and "fast-included" exons (type II). Many rate-sensitive exons are misspliced in tumors. Unexpectedly, slow and fast elongation often both increased or both decreased inclusion of a particular exon or retained intron. These results suggest that an optimal rate of transcriptional elongation is required for normal cotranscriptional pre-mRNA splicing.

| S-EPMC4248296 | biostudies-literature

Global impact of RNA polymerase II elongation inhibition on alternative splicing regulation.

Project description:The rate of RNA polymerase II (Pol II) elongation can influence splice site selection in nascent transcripts, yet the extent and physiological relevance of this kinetic coupling between transcription and alternative splicing (AS) is not well understood. We performed experiments to perturb Pol II elongation and then globally compared AS patterns with genome-wide Pol II occupancy. RNA binding and RNA processing functions were significantly enriched among the genes with Pol II elongation inhibition-dependent changes in AS. Under conditions that interfere with Pol II elongation, including cell stress, increased Pol II occupancy was detected in the intronic regions flanking the alternative exons in these genes, and these exons generally became more included. A disproportionately high fraction of these exons introduced premature termination codons that elicited nonsense-mediated mRNA decay (NMD), thereby further reducing transcript levels. Our results provide evidence that kinetic coupling between transcription, AS, and NMD affords a rapid mechanism by which cells can respond to changes in growth conditions, including cell stress, to coordinate the levels of RNA processing factors with mRNA levels.

| S-EPMC3044853 | biostudies-literature

Pre-mRNA Splicing is Facilitated by an Optimal RNA Polymerase II Elongation Rate

Project description:Transcription and pre-mRNA alternative splicing was analyzed by in isogenic human HEK293 cell lines that inducibly express a-amanitin resistant mutants of the RNA polymerase II large subunit with slow and fast elongation rates. Alternative splicing was analyzed by, RNA-seq and RASL-seq of polyA+ RNA from a-amanitin treated cells; transcription elongation rate was analyzed by BrUTP-labelled GRO-seq of a-amanitin treated cells at time points after release from a DRB (5,6-dichloro-1-bold beta-D-ribofuranosylbenzimidazole) block.

2014-11-25 | E-GEOD-63375 | biostudies-arrayexpress

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