Environmental perturbations have large effects on both organismal and cellular traits, including gene expression, but the extent to which the environment affects RNA processing remains largely uncharacterized. Recent studies have identified a large number of genetic variants associated with variation in RNA processing that also have an important role in complex traits; yet we do not know in which contexts the different underlying isoforms are used. Here, we comprehensively characterized changes in RNA processing events across 89 environments in five human cell types and identified 15,300 event shifts (FDR = 15%) comprised of eight event types in over 4,000 genes. Many of these changes occur consistently in the same direction across conditions, indicative of global regulation by trans factors. Accordingly, we demonstrate that environmental modulation of splicing factor binding predicts shifts in intron retention, and that binding of transcription factors predicts shifts in alternative first exon (AFE) usage in response to specific treatments. We validated the mechanism hypothesized for AFE in two independent datasets. Using ATAC-seq, we found altered binding of 64 factors in response to selenium at sites of AFE shift, including ...Continue Reading
Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death
Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing
7SK snRNP/P-TEFb couples transcription elongation with alternative splicing and is essential for vertebrate development
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Accurate inference of transcription factor binding from DNA sequence and chromatin accessibility data
G Run-mediated recognition of proteolipid protein and DM20 5' splice sites by U1 small nuclear RNA is regulated by context and proximity to the splice site.
The emerging role of pre-messenger RNA splicing in stress responses: sending alternative messages and silent messengers
Classification of human genomic regions based on experimentally determined binding sites of more than 100 transcription-related factors
Position-dependent splicing activation and repression by SR and hnRNP proteins rely on common mechanisms
Differential microRNA regulation correlates with alternative polyadenylation pattern between breast cancer and normal cells
Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position
Impaired nuclear translocation of the glucocorticoid receptor in corticosteroid-insensitive airway smooth muscle in severe asthma
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eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS-identified asthma genes
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The transcriptional and splicing landscape of intestinal organoids undergoing nutrient starvation or endoplasmic reticulum stress
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Widespread Shortening of 3' Untranslated Regions and Increased Exon Inclusion Are Evolutionarily Conserved Features of Innate Immune Responses to Infection
Parental vitamin deficiency affects the embryonic gene expression of immune-, lipid transport- and apolipoprotein genes
Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms
Novel mechanisms of regulation of the expression and transcriptional activity of hepatocyte nuclear factor 4α
Alternative splicing is highly variable among Daphnia pulex lineages in response to acute copper exposure.
Next-generation sequencing of DNA from resting eggs: signatures of eutrophication in a lake's sediment.
CZI Human Cell Atlas Seed Network
The aim of the Human Cell Atlas (HCA) is to build reference maps of all human cells in order to enhance our understanding of health and disease. The Seed Networks for the HCA project aims to bring together collaborators with different areas of expertise in order to facilitate the development of the HCA. Find the latest research from members of the HCA Seed Networks here.