Alternative splicing is a crucial step of the gene expression process in eukaryotes. It is a major cause for protein diversity and plays critical roles in differentiation, development, and disease. The studies on the mechanism of alternative splicing have traditionally focused on RNA sequence elements and their related splicing factors, but recent groundbreaking studies have shown that epigenetic factors play a key role in alternative splicing regulation. DNA methylation, chromatin structure and histone modifications interact with each other and regulate the process of alternative pre-mRNA splicing, forming a large and complex regulatory network. These findings suggest that epigenetic regulation not only determines the initiation of gene expression but also influences the outcome of pre-mRNA splicing. This review mainly focuses on the recent research progress in epigenetic regulation of pre-mRNA alternative splicing, including the functions of DNA methylation, chromatin structure and histone modifications in pre-mRNA alternative splicing, and speculates on its far-reaching effects on the study of human disease.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells.
Nat Commun
January 2025
Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.
View Article and Find Full Text PDFEffects of acute PM purification on cognitive function and underlying mechanisms: Evidence from integrating alternative splicing into multi-omics.
J Hazard Mater
January 2025
Vanke School of Public Health, Tsinghua University, Beijing 100084, China; Institute for Healthy China, Tsinghua University, Beijing 100084, China. Electronic address:
The relationship between fine particulate matter (PM) and cognition has been extensively investigated. However, the causal impact of acute PM purification on cognition improvement and the underlying biological mechanisms remain relatively opaque. Our double-blinded randomized controlled trial assessed the impact of acute PM purification on executive function, underpinned by multi-omics approaches including alternative splicing (AS) analysis.
View Article and Find Full Text PDFAberrant acetylation caused by a CDYL splicing mutation contributes to thin mid-piece related asthenoteratozoospermia and male infertility.
Andrology
January 2025
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Objectives: Acetylated tubulin is a hallmark of flagellar stability in spermatozoa, and studies have demonstrated the ability of CDYL to function as a tubulin acetyltransferase in spermatozoa. Of note, germline conditional knockout of Cdyl can lead to asthenoteratozoospermia and infertility in male mice. However, the role of CDYL gene in human fertility remains uncharacterized.
View Article and Find Full Text PDFImpact of rare non-coding variants on human diseases through alternative polyadenylation outliers.
Nat Commun
January 2025
Institute of Systems and Physical Biology, Shenzhen Bay Laboratory, Shenzhen, China.
Although rare non-coding variants (RVs) play crucial roles in complex traits and diseases, understanding their mechanisms and identifying disease-associated RVs continue to be major challenges. Here we constructed a comprehensive atlas of alternative polyadenylation (APA) outliers (aOutliers), including 1334 3' UTR and 200 intronic aOutliers, from 15,201 samples across 49 human tissues. These aOutliers exhibit unique characteristics from transcription or splicing outliers, with a pronounced RV enrichment.
View Article and Find Full Text PDFCoordinated neuron-specific splicing events restrict nucleosome engagement of the LSD1 histone demethylase complex.
Cell Rep
January 2025
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
Chromatin regulatory proteins are expressed broadly and assumed to exert the same intrinsic function across cell types. Here, we report that 14 chromatin regulators undergo evolutionary-conserved neuron-specific splicing events involving microexons. Among them are two components of a histone demethylase complex: LSD1 H3K4 demethylase and the H3K4me0-reader PHF21A.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!