ArticlePLoS biology2023
TDP-43 and other hnRNPs regulate cryptic exon inclusion of a key ALS/FTD risk gene, UNC13A.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- A molecular systems architecture of neuromuscular junction in amyotrophic lateral sclerosis.NPJ systems biology and applications · 2025Pooled it
- The UNC13A cryptic exon associates with cognitive impairment in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- TDP43 and hnRNP K Regulate Alternative Splicing of DNAJC5.Cell biology international · 2026Article
- Preservation of miR-9-5p and miR-124-3p in ALS-resistant oculomotor neurons contrasts with their downregulation in vulnerable spinal motor neurons, irrespective of TDP-43 pathology.Acta neuropathologica · 2026Article
- From development to disease: the neuronal role of hnRNPs through the lens ofFrontiers in cell and developmental biology · 2026Review
- Transcriptomic and pathological analysis of the hnRNP network reveals glial involvement in frontotemporal lobar degeneration pathological subtypes.Brain communications · 2026Article
- Global research architecture of RNA-binding proteins in neurodegenerative diseases: a web of science bibliometric study with PubMed record verification, 2001-2025.Frontiers in aging neuroscience · 2026Article
- TDP-43 promotes efficient HSV-1 replication in human DRG-derived neurons.Journal of virology · 2025Article
- Article
- Single-nucleus transcriptome atlas of orbitofrontal cortex in ALS with a deep learning-based decoding of alternative polyadenylation mechanisms.Cell genomics · 2025Article
- Decoding ALS from the tail end of RNA.Cell genomics · 2025Article
- Sensitivity to TDP-43 loss and degradation resistance determine cryptic exon biomarker potential.bioRxiv : the preprint server for biology · 2025Article
- DNA methylation-wide association study of prevalent and incident dementia in the US Health and Retirement Study.medRxiv : the preprint server for health sciences · 2025Article
- Intrinsically accelerated cellular degradation is amplified by TDP-43 loss in ALS-vulnerable motor neurons in a zebrafish model.Nature communications · 2025Article
- Munc13-1 restoration mitigates presynaptic pathology in spinal muscular atrophy.Nature communications · 2025Article
- Cryptic Splicing of GAP43 mRNA is a Novel Hallmark of TDP-43-Associated ALS and AD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- ALS-associated RNA-binding proteins promote UNC13A transcription through REST downregulation.The EMBO journal · 2025Article
- Sporadic ALS induced pluripotent stem cell derived neurons reveal hallmarks of TDP-43 loss of function.Nature communications · 2025Article
- Mitochondria and Endoplasmic Reticulum Contact Site as a Regulator of Proteostatic Stress Responses in Neurodegenerative Diseases.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
A major function of TAR DNA-binding protein-43 (TDP-43) is to repress the inclusion of cryptic exons during RNA splicing. One of these cryptic exons is in UNC13A, a genetic risk factor for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The accumulation of cryptic UNC13A in disease is heightened by the presence of a risk haplotype located within the cryptic exon itself. Here, we revealed that TDP-43 extreme N-terminus is important to repress UNC13A cryptic exon inclusion. Further, we found hnRNP L, hnRNP A1, and hnRNP A2B1 bind UNC13A RNA and repress cryptic exon inclusion, independently of TDP-43. Finally, higher levels of hnRNP L protein associate with lower burden of UNC13A cryptic RNA in ALS/FTD brains. Our findings suggest that while TDP-43 is the main repressor of UNC13A cryptic exon inclusion, other hnRNPs contribute to its regulation and may potentially function as disease modifiers.
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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.