ArticleNucleic acids research2017
Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 56 citations in OpenAlex.
- hnRNP H controls alternative splicing of human papillomavirus type 16 E1, E6, E7, and E6^E7 mRNAs via GGG motifs.Journal of virology · 2024Article
- Alternative splicing of a chromatin modifier alters the transcriptional regulatory programs of stem cell maintenance and neuronal differentiation.Cell stem cell · 2024Article
- Non-canonical isoforms of the mRNA polyadenylation factor WDR33 regulate STING-mediated immune responses.Cell reports · 2024Article
- Post-transcriptional regulation of the transcriptional apparatus in neuronal development.Frontiers in molecular neuroscience · 2024Review
- Alternative Transcripts Diversify Genome Function for Phenome Relevance to Health and Diseases.Genes · 2023Review
- Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction.iScience · 2023Article
- Changes in the Acetylcholinesterase Enzymatic Activity in Tumor Development and Progression.Cancers · 2023Review
- Review
- Macrophage differentiation is marked by increased abundance of the mRNA 3' end processing machinery, altered poly(A) site usage, and sensitivity to the level of CstF64.Frontiers in immunology · 2023Article
- SRSF3 and HNRNPH1 Regulate Radiation-Induced Alternative Splicing of Protein Arginine Methyltransferase 5 in Hepatocellular Carcinoma.International journal of molecular sciences · 2022Article
- Deciphering the impact of genetic variation on human polyadenylation using APARENT2.Genome biology · 2022Article
- The transcriptional terminator XRN2 and the RNA-binding protein Sam68 link alternative polyadenylation to cell cycle progression in prostate cancer.Nature structural & molecular biology · 2022Article
- Alternative splicing and alternative polyadenylation define tumor immune microenvironment and pharmacogenomic landscape in clear cell renal carcinoma.Molecular therapy. Nucleic acids · 2022Article
- Distinct roles of hnRNPH1 low-complexity domains in splicing and transcription.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The three as: Alternative splicing, alternative polyadenylation and their impact on apoptosis in immune function.Immunological reviews · 2021Review
- PRMT1-dependent regulation of RNA metabolism and DNA damage response sustains pancreatic ductal adenocarcinoma.Nature communications · 2021Article
- The RNA-binding protein Igf2bp3 is critical for embryonic and germline development in zebrafish.PLoS genetics · 2021Article
- Multiple ways to a dead end: diverse mechanisms by which ALS mutant genes induce cell death.Cell cycle (Georgetown, Tex.) · 2021Review
- The role of hnRNPs in frontotemporal dementia and amyotrophic lateral sclerosis.Acta neuropathologica · 2020Review
- A missense mutation in the CSTF2 gene that impairs the function of the RNA recognition motif and causes defects in 3' end processing is associated with intellectual disability in humans.Nucleic acids research · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
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Abstract
Acetylcholinesterase (AChE), encoded by the ACHE gene, hydrolyzes the neurotransmitter acetylcholine to terminate synaptic transmission. Alternative splicing close to the 3΄ end generates three distinct isoforms of AChET, AChEH and AChER. We found that hnRNP H binds to two specific G-runs in exon 5a of human ACHE and activates the distal alternative 3΄ splice site (ss) between exons 5a and 5b to generate AChET. Specific effect of hnRNP H was corroborated by siRNA-mediated knockdown and artificial tethering of hnRNP H. Furthermore, hnRNP H competes for binding of CstF64 to the overlapping binding sites in exon 5a, and suppresses the selection of a cryptic polyadenylation site (PAS), which additionally ensures transcription of the distal 3΄ ss required for the generation of AChET. Expression levels of hnRNP H were positively correlated with the proportions of the AChET isoform in three different cell lines. HnRNP H thus critically generates AChET by enhancing the distal 3΄ ss and by suppressing the cryptic PAS. Global analysis of CLIP-seq and RNA-seq also revealed that hnRNP H competitively regulates alternative 3΄ ss and alternative PAS in other genes. We propose that hnRNP H is an essential factor that competitively regulates alternative splicing and alternative polyadenylation.
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