ArticlePLoS genetics2017
Environmental perturbations lead to extensive directional shifts in RNA processing.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Sex differences in molecular pathways underlying cardiovascular health in Black Americans.Research square · 2026Article
- mRNA initiation and termination are spatially coordinated.Science (New York, N.Y.) · 2025Article
- The generation and consequences of N-terminal proteoform diversity.Cell reports · 2025Review
- High-resolution profiling reveals coupled transcriptional and translational regulation of transgenes.Nucleic acids research · 2025Article
- High-resolution profiling reveals coupled transcriptional and translational regulation of transgenes.bioRxiv : the preprint server for biology · 2024Article
- Profiling genetically driven alternative splicing across the Indonesian archipelago.American journal of human genetics · 2024Article
- Differences in alternative splicing events in the adaptive strategies of two Daphnia galeata genotypes induced by fish kairomones.BMC genomics · 2024Article
- Genotype × environment interactions in gene regulation and complex traits.Nature genetics · 2024Review
- mRNA initiation and termination are spatially coordinated.bioRxiv : the preprint server for biology · 2024Article
- Article
- Mapping of promoter usage QTL using RNA-seq data reveals their contributions to complex traits.PLoS computational biology · 2022Article
- Altered genome-wide hippocampal gene expression profiles following early life lead exposure and their potential for reversal by environmental enrichment.Scientific reports · 2022Article
- Secondhand smoke affects reproductive functions by altering the mouse testis transcriptome, and leads to select intron retention in Pde1a.Environment international · 2022Article
- Out-of-Equilibrium Biophysical Chemistry: The Case for Multidimensional, Integrated Single-Molecule Approaches.The journal of physical chemistry. B · 2021Article
- Article
- The Atypical Kinase RIOK3 Limits RVFV Propagation and Is Regulated by Alternative Splicing.Viruses · 2021Article
- Alterations of RNA splicing patterns in esophagus squamous cell carcinoma.Cell & bioscience · 2021Article
- Global Transcriptomics Uncovers Distinct Contributions From Splicing Regulatory Proteins to the Macrophage Innate Immune Response.Frontiers in immunology · 2021Article
- Alternative splicing is highly variable among Daphnia pulex lineages in response to acute copper exposure.BMC genomics · 2020Article
- Defining the genetic and evolutionary architecture of alternative splicing in response to infection.Nature communications · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
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 ELF2 and other factors in the ETS family. We also performed AFE QTL mapping in 373 individuals and found an enrichment for SNPs predicted to disrupt binding of the ELF2 factor. Together, these results demonstrate that RNA processing is dramatically changed in response to environmental perturbations through specific mechanisms regulated by trans factors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.