ArticleNucleic acids research2024
Conserved intronic secondary structures with concealed branch sites regulate alternative splicing of poison exons.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- The RNA structural code: orchestrating gene expression and enabling precision therapies.Acta pharmacologica Sinica · 2026Review
- ZRANB1 promotes cell proliferation and lymph node metastasis through SF3B3-mediated alternative splicing of CHEK2 in urothelial bladder cancer.Cell death & disease · 2026Article
- An in vivo parallelized reporter assay to uncover tissue-specific splicing regulatory sequences in a multicellular animal.Nucleic acids research · 2026Article
- An ultraconserved pseudo 5' splice site fine-tunes development by regulating alternative splicing within TOR-related pathways.Nature communications · 2026Article
- Mechanism of alternative splicing of yeast HEH1 through competing 5' splice sites.Nature communications · 2025Article
- Precursor RNA structural patterns at SF3B1 mutation sensitive cryptic 3' splice sites.RNA biology · 2025Article
- Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Control of gene output by intron RNA structure.bioRxiv : the preprint server for biology · 2025Article
- Splicing factor Sf3b1 facilitates maintenance of neuronal dendrites by modulating mitochondrial health.Cellular and molecular life sciences : CMLS · 2025Article
- Angel wing: a class of alternative splicing regulators in animals.Nucleic acids research · 2025Article
- Rapid folding of nascent RNA regulates eukaryotic RNA biogenesis.Molecular cell · 2025Article
- Transcriptome-wide prediction of heat-sensitive RNA structures inFrontiers in plant science · 2025Article
- RNA structure in alternative splicing regulation: from mechanism to therapy.Acta biochimica et biophysica Sinica · 2024Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Alternative splicing (AS) generates multiple RNA isoforms and increases the complexities of transcriptomes and proteomes. However, it remains unclear how RNA structures contribute to AS regulation. Here, we systematically search transcriptomes for secondary structures with concealed branch sites (BSs) in the alternatively spliced introns and predict thousands of them from six organisms, of which many are evolutionarily conserved. Intriguingly, a highly conserved stem-loop structure with concealed BSs is found in animal SF3B3 genes and colocalizes with a downstream poison exon (PE). Destabilization of this structure allows increased usage of the BSs and results in enhanced PE inclusion in human and Drosophila cells, leading to decreased expression of SF3B3. This structure is experimentally validated using an in-cell SHAPE-MaP assay. Through RNA interference screens of 28 RNA-binding proteins, we find that this stem-loop structure is sensitive to U2 factors. Furthermore, we find that SF3B3 also facilitates DNA repair and protects genome stability by enhancing interaction between ERCC6/CSB and arrested RNA polymerase II. Importantly, both Drosophila and human cells with the secondary structure mutated by genome editing exhibit altered DNA repair in vivo. This study provides a novel and common mechanism for AS regulation of PEs and reveals a physiological function of SF3B3 in DNA repair.
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