ArticleNature communications2024
hnRNP A1 dysfunction alters RNA splicing and drives neurodegeneration in multiple sclerosis (MS).
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- The role of AI-assisted drug repurposing in neurological disorders: a systematic review of validation strategies, challenges and opportunities.Journal of nanobiotechnology · 2026Pooled it
- CRISPR and Myelin regeneration: a systematic review of applications in demyelinating CNS Disorders, with a focus on MS.Regenerative medicine · 2025Pooled it
- Betaine alleviates renal osteodystrophy by stabilizing ABCG1 mRNA to inhibit HMOX1-mediated ferroptosis in BMSCs.Genes & diseases · 2027Article
- Integrative Multi-Omics Analysis of Multiple Sclerosis Reveals Cell-Type-Specific Regulatory Landscapes and Discordant Methylation-Expression Coupling.International journal of molecular sciences · 2026Article
- Mammalian aging involves genome-wide splicing degeneration leading to functional decline.bioRxiv : the preprint server for biology · 2026Article
- Novel truncating Desmin mutation Arg150Stop disrupts structural integrity and cellular homeostasis by formation of persistent aggregate-like structure.Cell death discovery · 2026Article
- Increased VH4+JH6+ antibody heavy chain use in plasmablasts from asymptomatic multiple sclerosis patients.Genes and immunity · 2026Article
- RNArchitects: how hnRNPs shape neuronal landscapes.Brain : a journal of neurology · 2026Review
- RNA-binding proteins: a comprehensive review of multifaceted regulatory mechanisms in neuroinflammation and implications in the pathogenesis of neurological disorders.Journal of neuroinflammation · 2026Review
- Transcriptome analysis of the prefrontal cortex identifies inflammatory genes associated with cognitive impairment in a model of multiple sclerosis.Cell death discovery · 2026Article
- Elucidating the Causal Relationships Between B Cells, Dendritic Cells, and Multiple Sclerosis Pathogenesis.Brain and behavior · 2026Article
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- RNA-Binding Proteins in Adipose Biology: From Mechanistic Understanding to Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Splicing-based biomarkers define a robust multigene classifier for relapsing-remitting multiple sclerosis.Journal of translational autoimmunity · 2025Article
- The mCells · 2025Review
- Proteomic signatures and mitochondrial dysfunctions in peripheral T cells reveal novel ınsights into Alzheimer's disease.Scientific reports · 2025Article
- Epididymal dynamics and preimplantation roles of a sperm-enriched 5' fragment of tRNA-valine.Cell reports · 2025Article
- Splicing factor Sf3b1 facilitates maintenance of neuronal dendrites by modulating mitochondrial health.Cellular and molecular life sciences : CMLS · 2025Article
- Systematic Analysis of Alternative Splicing in Transcriptomes of Multiple Sclerosis Patient Brain Samples.International journal of molecular sciences · 2025Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurodegeneration is the primary driver of disease progression in multiple sclerosis (MS) resulting in permanent disability, creating an urgent need to discover its underlying mechanisms. Herein, we establish that dysfunction of the RNA binding protein heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) results in differential of binding to RNA targets causing alternative RNA splicing, which contributes to neurodegeneration in MS and its models. Using RNAseq of MS brains, we discovered differential expression and aberrant splicing of hnRNP A1 target RNAs involved in neuronal function and RNA homeostasis. We confirmed this in vivo in experimental autoimmune encephalomyelitis employing CLIPseq specific for hnRNP A1, where hnRNP A1 differentially binds and regulates RNA, including aberrantly spliced targets identified in human samples. Additionally, dysfunctional hnRNP A1 expression in neurons caused neurite loss and identical changes in splicing, corroborating hnRNP A1 dysfunction as a cause of neurodegeneration. Collectively, these data indicate hnRNP A1 dysfunction causes altered neuronal RNA splicing, resulting in neurodegeneration in MS.
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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.