ArticlePLoS genetics2012
Muscle-specific splicing factors ASD-2 and SUP-12 cooperatively switch alternative pre-mRNA processing patterns of the ADF/cofilin gene in Caenorhabditis elegans.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
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- TDP43 promotes stemness of breast cancer stem cells through CD44 variant splicing isoforms.Cell death & disease · 2022Article
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- Dietary restriction induces posttranscriptional regulation of longevity genes.Life science alliance · 2019Article
- ALG-1 Influences Accurate mRNA Splicing Patterns in theGenetics · 2019Article
- Alternative splicing of the Caenorhabditis elegans lev-11 tropomyosin gene is regulated in a tissue-specific manner.Cytoskeleton (Hoboken, N.J.) · 2018Article
- RNA Binding Protein RBM38 Regulates Expression of the 11-Kilodalton Protein of Parvovirus B19, Which Facilitates Viral DNA Replication.Journal of virology · 2018Article
- Loss of TDP43 inhibits progression of triple-negative breast cancer in coordination with SRSF3.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The combinatorial control of alternative splicing in C. elegans.PLoS genetics · 2017Article
- RBM24 promotes U1 snRNP recognition of the mutated 5' splice site in theRNA (New York, N.Y.) · 2017Article
- Ancient antagonism between CELF and RBFOX families tunes mRNA splicing outcomes.Genome research · 2017Article
- Protein 4.1R Exon 16 3' Splice Site Activation Requires Coordination among TIA1, Pcbp1, and RBM39 during Terminal Erythropoiesis.Molecular and cellular biology · 2017Article
- Developmental regulation of RNA processing by Rbfox proteins.Wiley interdisciplinary reviews. RNA · 2017Review
- Evolutionarily conserved autoregulation of alternative pre-mRNA splicing by ribosomal protein L10a.Nucleic acids research · 2016Article
- Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Pre-mRNAs are often processed in complex patterns in tissue-specific manners to produce a variety of protein isoforms from single genes. However, mechanisms orchestrating the processing of the entire transcript are not well understood. Muscle-specific alternative pre-mRNA processing of the unc-60 gene in Caenorhabditis elegans, encoding two tissue-specific isoforms of ADF/cofilin with distinct biochemical properties in regulating actin organization, provides an excellent in vivo model of complex and tissue-specific pre-mRNA processing; it consists of a single first exon and two separate series of downstream exons. Here we visualize the complex muscle-specific processing pattern of the unc-60 pre-mRNA with asymmetric fluorescence reporter minigenes. By disrupting juxtaposed CUAAC repeats and UGUGUG stretch in intron 1A, we demonstrate that these elements are required for retaining intron 1A, as well as for switching the processing patterns of the entire pre-mRNA from non-muscle-type to muscle-type. Mutations in genes encoding muscle-specific RNA-binding proteins ASD-2 and SUP-12 turned the colour of the unc-60 reporter worms. ASD-2 and SUP-12 proteins specifically and cooperatively bind to CUAAC repeats and UGUGUG stretch in intron 1A, respectively, to form a ternary complex in vitro. Immunohistochemical staining and RT-PCR analyses demonstrate that ASD-2 and SUP-12 are also required for switching the processing patterns of the endogenous unc-60 pre-mRNA from UNC-60A to UNC-60B in muscles. Furthermore, systematic analyses of partially spliced RNAs reveal the actual orders of intron removal for distinct mRNA isoforms. Taken together, our results demonstrate that muscle-specific splicing factors ASD-2 and SUP-12 cooperatively promote muscle-specific processing of the unc-60 gene, and provide insight into the mechanisms of complex pre-mRNA processing; combinatorial regulation of a single splice site by two tissue-specific splicing regulators determines the binary fate of the entire transcript.
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Registered trials
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