ArticleNeuron2022
Suppression of premature transcription termination leads to reduced mRNA isoform diversity and neurodegeneration.
Article in Neuron, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Transcriptional readthrough progresses from incidental byproduct to therapeutic opportunity.Nature structural & molecular biology · 2026Article
- Regulation of gene expression by alternative polyadenylation in health and disease.Nature reviews. Genetics · 2026Review
- Enzymology of the metazoan tRNA ligase complex: a lifetime in cycles.Cellular and molecular life sciences : CMLS · 2026Review
- Impact of the CYFIP2 R87C variant in a human neuronal model in vitro.Scientific reports · 2026Article
- Article
- TDP-43 loss induces cryptic polyadenylation in ALS/FTD.Nature neuroscience · 2025Article
- The paradox of R-loops: guardians of the genome or drivers of disease?Genome research · 2025Review
- Fateful Decisions of Where to Cut the Line: Pathology Associated with Aberrant 3' End Processing and Transcription Termination.Journal of molecular biology · 2025Review
- Evaluation of the Patients with the Diagnosis of Pontocerebellar Hypoplasia: A Multicenter National Study.Cerebellum (London, England) · 2024Article
- Comprehensive transcriptome analysis reveals altered mRNA splicing and post-transcriptional changes in the aged mouse brain.Nucleic acids research · 2024Article
- CPSF3 inhibition blocks pancreatic cancer cell proliferation through disruption of core histone mRNA processing.RNA (New York, N.Y.) · 2024Article
- New insights into RNA processing by the eukaryotic tRNA splicing endonuclease.The Journal of biological chemistry · 2023Review
- Structural basis for pre-tRNA recognition and processing by the human tRNA splicing endonuclease complex.Nature structural & molecular biology · 2023Article
- Alternative polyadenylation alters protein dosage by switching between intronic and 3'UTR sites.Science advances · 2023Article
- Prematurely terminated intron-retaining mRNAs invade axons in SFPQ null-driven neurodegeneration and are a hallmark of ALS.Nature communications · 2022Article
- mRNA isoform balance in neuronal development and disease.Wiley interdisciplinary reviews. RNAReview
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Tight regulation of mRNA isoform expression is essential for neuronal development, maintenance, and function; however, the repertoire of proteins that govern isoform composition and abundance remains incomplete. Here, we show that the RNA kinase CLP1 regulates mRNA isoform expression through suppression of proximal cleavage and polyadenylation. We found that human stem-cell-derived motor neurons without CLP1 or with the disease-associated CLP1 p.R140H variant had distinct patterns of RNA-polymerase-II-associated cleavage and polyadenylation complex proteins that correlated with polyadenylation site usage. These changes resulted in imbalanced mRNA isoform expression of long genes important for neuronal function that were recapitulated in vivo. Strikingly, we observed the same pattern of reduced mRNA isoform diversity in 3' end sequencing data from brain tissues of patients with neurodegenerative disease. Together, our results identify a previously uncharacterized role for CLP1 in mRNA 3' end formation and reveal an mRNA misprocessing signature in neurodegeneration that may suggest a common mechanism of disease.
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