ArticleHuman molecular genetics2016
Extensive cryptic splicing upon loss of RBM17 and TDP43 in neurodegeneration models.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 114 citations in OpenAlex.
- CRYSPER and CUREIPES: two new molecular tools enabling analysis of RNA splicing and C-to-U RNA editing-inducible protein expression at single cell resolution.Nucleic acids research · 2026Article
- 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
- A next-generation HDAC6 inhibitor for amyotrophic lateral sclerosis and frontotemporal dementia.Brain : a journal of neurology · 2026Article
- Misregulated alternative splicing in endometriosis: a role for aberrant mRNA variants in endometriotic cell growth.Cell death discovery · 2026Article
- Article
- MicroRNAs and Long Non-Coding RNAs Affect the Mechanisms Involved in Age-Related Neurodegeneration in a Manner Depending on RNA-Binding Proteins.Molecular neurobiology · 2026Review
- Aberrant NSUN1 activity connects mLife science alliance · 2026Article
- Symptomatic treatment by a BBB-permeable AAV engineered to restore TDP-43 function slows motor neuron disease and prevents paralysis.bioRxiv : the preprint server for biology · 2025Article
- Large-scale RNA-Seq mining reveals ciclopirox olamine induces TDP-43 cryptic exons.Nature communications · 2025Article
- Altered mRNA transport and local translation in iNeurons with RNA binding protein knockdown.bioRxiv : the preprint server for biology · 2024Article
- Multivalent GU-rich oligonucleotides sequester TDP-43 in the nucleus by inducing high molecular weight RNP complexes.iScience · 2024Article
- Elevated nuclear TDP-43 induces constitutive exon skipping.Molecular neurodegeneration · 2024Article
- The pathogenic mechanism of TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis.Neural regeneration research · 2024Review
- A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS-FTD.Nature medicine · 2024Article
- Fluid biomarkers for amyotrophic lateral sclerosis: a review.Molecular neurodegeneration · 2024Review
- hnRNP A1 dysfunction alters RNA splicing and drives neurodegeneration in multiple sclerosis (MS).Nature communications · 2024Article
- Dysregulation of alternative splicing in spinocerebellar ataxia type 1.Human molecular genetics · 2024Article
- Loss of TDP-43 splicing repression occurs early in the aging population and is associated with Alzheimer's disease neuropathologic changes and cognitive decline.Acta neuropathologica · 2023Article
- Cryptic exon detection and transcriptomic changes revealed in single-nuclei RNA sequencing of C9ORF72 patients spanning the ALS-FTD spectrum.Acta neuropathologica · 2023Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Splicing regulation is an important step of post-transcriptional gene regulation. It is a highly dynamic process orchestrated by RNA-binding proteins (RBPs). RBP dysfunction and global splicing dysregulation have been implicated in many human diseases, but the in vivo functions of most RBPs and the splicing outcome upon their loss remain largely unexplored. Here we report that constitutive deletion of Rbm17, which encodes an RBP with a putative role in splicing, causes early embryonic lethality in mice and that its loss in Purkinje neurons leads to rapid degeneration. Transcriptome profiling of Rbm17-deficient and control neurons and subsequent splicing analyses using CrypSplice, a new computational method that we developed, revealed that more than half of RBM17-dependent splicing changes are cryptic. Importantly, RBM17 represses cryptic splicing of genes that likely contribute to motor coordination and cell survival. This finding prompted us to re-analyze published datasets from a recent report on TDP-43, an RBP implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), as it was demonstrated that TDP-43 represses cryptic exon splicing to promote cell survival. We uncovered a large number of TDP-43-dependent splicing defects that were not previously discovered, revealing that TDP-43 extensively regulates cryptic splicing. Moreover, we found a significant overlap in genes that undergo both RBM17- and TDP-43-dependent cryptic splicing repression, many of which are associated with survival. We propose that repression of cryptic splicing by RBPs is critical for neuronal health and survival. CrypSplice is available at www.liuzlab.org/CrypSplice.
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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.