ArticleNucleic acids research2016
Nuclear poly(A)-binding protein aggregates misplace a pre-mRNA outside of SC35 speckle causing its abnormal splicing.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- U2AF1 modulates alternative exon selection and guards zygotic splicing activation in mouse preimplantation embryogenesis.Cellular and molecular life sciences : CMLS · 2026Article
- Maternal TDP43 orchestrates nuclear speckle assembly and zygotic splicing activation during oocyte-to-embryo transition in mice.Nucleic acids research · 2026Article
- Article
- Midfacial toddler excoriation syndrome (MiTES): case series, diagnostic criteria and evidence for a pathogenic mechanism.The British journal of dermatology · 2024Article
- The small compound Icerguastat reduces muscle defects in oculopharyngeal muscular dystrophy through the PERK pathway of the unfolded protein response.Open biology · 2023Article
- Assessment of PABPN1 nuclear inclusions on a large cohort of patients and in a human xenograft model of oculopharyngeal muscular dystrophy.Acta neuropathologica · 2022Article
- MPP6 stimulates both RRP6 and DIS3 to degrade a specified subset of MTR4-sensitive substrates in the human nucleus.Nucleic acids research · 2022Article
- Activation of the ubiquitin-proteasome system contributes to oculopharyngeal muscular dystrophy through muscle atrophy.PLoS genetics · 2022Article
- Pharyngeal pathology in a mouse model of oculopharyngeal muscular dystrophy is associated with impaired basal autophagy in myoblasts.Frontiers in cell and developmental biology · 2022Article
- Anti-prion Drugs Targeting the Protein Folding Activity of the Ribosome Reduce PABPN1 Aggregation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Troponin Variants as Markers of Skeletal Muscle Health and Diseases.Frontiers in physiology · 2021Review
- Lamin A safeguards the mAging cell · 2020Article
- Established PABPN1 intranuclear inclusions in OPMD muscle can be efficiently reversed by AAV-mediated knockdown and replacement of mutant expanded PABPN1.Human molecular genetics · 2019Article
- The nuclear GSK-3β regulated post-transcriptional processing of mRNA through phosphorylation of SC35.Molecular and cellular biochemistry · 2019Article
- Post-transcriptional regulation of Pabpn1 by the RNA binding protein HuR.Nucleic acids research · 2018Article
- Accumulation of poly(A) RNA in nuclear granules enriched in Sam68 in motor neurons from the SMNΔ7 mouse model of SMA.Scientific reports · 2018Article
- Nuclear poly(A) binding protein 1 (PABPN1) and Matrin3 interact in muscle cells and regulate RNA processing.Nucleic acids research · 2017Article
- Nuclear speckles: molecular organization, biological function and role in disease.Nucleic acids research · 2017Review
- Novel mouse models of oculopharyngeal muscular dystrophy (OPMD) reveal early onset mitochondrial defects and suggest loss of PABPN1 may contribute to pathology.Human molecular genetics · 2017Article
- Functional impact of an oculopharyngeal muscular dystrophy mutation in PABPN1.The Journal of physiology · 2017Article
Corrections and comments
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Authors and funding
17 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A short abnormal polyalanine expansion in the polyadenylate-binding protein nuclear-1 (PABPN1) protein causes oculopharyngeal muscular dystrophy (OPMD). Mutated PABPN1 proteins accumulate as insoluble intranuclear aggregates in muscles of OPMD patients. While the roles of PABPN1 in nuclear polyadenylation and regulation of alternative poly(A) site choice have been established, the molecular mechanisms which trigger pathological defects in OPMD and the role of aggregates remain to be determined. Using exon array, for the first time we have identified several splicing defects in OPMD. In particular, we have demonstrated a defect in the splicing regulation of the muscle-specific Troponin T3 (TNNT3) mutually exclusive exons 16 and 17 in OPMD samples compared to controls. This splicing defect is directly linked to the SC35 (SRSF2) splicing factor and to the presence of nuclear aggregates. As reported here, PABPN1 aggregates are able to trap TNNT3 pre-mRNA, driving it outside nuclear speckles, leading to an altered SC35-mediated splicing. This results in a decreased calcium sensitivity of muscle fibers, which could in turn plays a role in muscle pathology. We thus report a novel mechanism of alternative splicing deregulation that may play a role in various other diseases with nuclear inclusions or foci containing an RNA binding protein.
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