ArticleNature communications2022
Multilayered regulations of alternative splicing, NMD, and protein stability control temporal induction and tissue-specific expression of TRIM46 during axon formation.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Alternatively Spliced Dual-Coding Regions Contribute to the Human Gene Regulatory Program.bioRxiv : the preprint server for biology · 2026Article
- The implications of alternative splicing regulation for maximum lifespan.Nature communications · 2025Article
- The Role of mRNA Alternative Processing in Mammalian Neurodevelopment.International journal of molecular sciences · 2025Review
- The Implications of Alternative Splicing Regulation for Maximum Lifespan.bioRxiv : the preprint server for biology · 2025Article
- Evaluating TRIM46's Role in Axon Initial Segment Formation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- TRIM46 Is Required for Microtubule Fasciculation In Vivo But Not Axon Specification or Axon Initial Segment Formation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- TRIM Proteins and Antiviral Microtubule Reorganization: A Novel Component in Innate Immune Responses?Viruses · 2024Review
- Translatome analysis in acute ischemic stroke: Astrocytes and microglia exhibit differences in poststroke alternative splicing of expressed transcripts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Alternative splicing in neurodegenerative disease and the promise of RNA therapies.Nature reviews. Neuroscience · 2023Review
- Article
- TheThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Pathology of Initial Axon Segments in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Related Disorders.International journal of molecular sciences · 2022Review
- mRNA isoform balance in neuronal development and disease.Wiley interdisciplinary reviews. RNAReview
- Article
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Authors and funding
4 authors at 2 institutions in 1 country.
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Abstract
The gene regulation underlying axon formation and its exclusiveness to neurons remains elusive. TRIM46 is postulated to determine axonal fate. We show Trim46 mRNA is expressed before axonogenesis, but TRIM46 protein level is inhibited by alternative splicing of two cassette exons coupled separately to stability controls of Trim46 mRNA and proteins, effectively inducing functional knockout of TRIM46 proteins. Exon 8 inclusion causes nonsense-mediated mRNA decay of Trim46 transcripts. PTBP2-mediated exon 10 skipping produces transcripts encoding unstable TRIM46 proteins. During axonogenesis, transcriptional activation, decreased exon 8 inclusion, and enhanced exon 10 inclusion converge to increase TRIM46 proteins, leading to its neural-specific expression. Genetic deletion of these exons alters TRIM46 protein levels and shows TRIM46 is instructive though not always required for AnkG localization nor a determinant of AnkG density. Therefore, two concurrently but independently regulated alternative exons orchestrate the temporal induction and tissue-specific expression of TRIM46 proteins to mediate axon formation.
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