ArticleProceedings of the National Academy of Sciences of the United States of America2015
Systematic discovery of regulated and conserved alternative exons in the mammalian brain reveals NMD modulating chromatin regulators.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 181 citations in OpenAlex.
- Ternary Neurexin-T178-PTPR complexes represent a pre-synaptic core-module of neuronal synapse organization.Nature communications · 2026Article
- Onconeural antigen NOVA1 dysregulates RNA alternative splicing in breast cancer.RNA (New York, N.Y.) · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- Alternative splicing-triggered mRNA decay informs splice-switching targets for neurodevelopmental disorders.The Journal of clinical investigation · 2026Article
- An ultraconserved pseudo 5' splice site fine-tunes development by regulating alternative splicing within TOR-related pathways.Nature communications · 2026Article
- A homozygous synonymous variant in SMG5, encoding a nonsense-mediated mRNA decay factor, causes developmental delay with growth retardation and relative macrocephaly.Human genetics · 2026Article
- A neuron type-specific microexon in Ank3/ankyrin-G modulates calcium activity and neuronal excitability.Nature communications · 2026Article
- Roles of NRXN1 in neuropsychiatric disorders: from genetic lesion to molecular mechanism.Frontiers in neuroscience · 2026Review
- Primate-specific adaptation of Ku protects transcriptomic integrity by suppressing Alu-mediated alternative splicing.bioRxiv : the preprint server for biology · 2025Article
- A neuron type-specific microexon inbioRxiv : the preprint server for biology · 2025Article
- Article
- Alternative splicing of the Snap23 microexon is regulated by MBNL, QKI, and RBFOX2 in a tissue-specific manner and is altered in striated muscle diseases.RNA biology · 2025Article
- Cas13d-mediated isoform-specific RNA knockdown with a unified computational and experimental toolbox.Nature communications · 2025Article
- Reverse engineering neuron-type-specific and type-orthogonal splicing-regulatory networks using diverse cellular transcriptomes.Cell reports · 2025Article
- No more nonsense: evaluating poison exons as therapeutic targets in neurodevelopmental disorders.Current opinion in genetics & development · 2025Review
- Isoform switch of T-cell factor7L2 during mouse heart development.Journal of molecular and cellular cardiology plus · 2025Article
- Ninein isoform contributions to intracellular processes and macrophage immune function.The Journal of biological chemistry · 2025Article
- Genetic and functional analysis of unproductive splicing using LeafCutter2.bioRxiv : the preprint server for biology · 2025Article
- Analysis of neurexin-neuroligin complexes supports an isoform-specific role for beta-neurexin-1 dysfunction in a mouse model of autism.Molecular brain · 2025Article
- A humanized NOVA1 splicing factor alters mouse vocal communications.Nature communications · 2025Article
60 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Alternative splicing (AS) dramatically expands the complexity of the mammalian brain transcriptome, but its atlas remains incomplete. Here we performed deep mRNA sequencing of mouse cortex to discover and characterize alternative exons with potential functional significance. Our analysis expands the list of AS events over 10-fold compared with previous annotations, demonstrating that 72% of multiexon genes express multiple splice variants in this single tissue. To evaluate functionality of the newly discovered AS events, we conducted comprehensive analyses on central nervous system (CNS) cell type-specific splicing, targets of tissue- or cell type-specific RNA binding proteins (RBPs), evolutionary selection pressure, and coupling of AS with nonsense-mediated decay (AS-NMD). We show that newly discovered events account for 23-42% of all cassette exons under tissue- or cell type-specific regulation. Furthermore, over 7,000 cassette exons are under evolutionary selection for regulated AS in mammals, 70% of which are new. Among these are 3,058 highly conserved cassette exons, including 1,014 NMD exons that may function directly to control gene expression levels. These NMD exons are particularly enriched in RBPs including splicing factors and interestingly also regulators for other steps of RNA metabolism. Unexpectedly, a second group of NMD exons reside in genes encoding chromatin regulators. Although the conservation of NMD exons in RBPs frequently extends into lower vertebrates, NMD exons in chromatin regulators are introduced later into the mammalian lineage, implying the emergence of a novel mechanism coupling AS and epigenetics. Our results highlight previously uncharacterized complexity and evolution in the mammalian brain transcriptome.
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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.