Reference - Detail
| RRC ID | 45535 |
|---|---|
| Author | Chen F, Zhou Y, Qi YB, Khivansara V, Li H, Chun SY, Kim JK, Fu XD, Jin Y. |
| Title | Context-dependent modulation of Pol II CTD phosphatase SSUP-72 regulates alternative polyadenylation in neuronal development. |
| Journal | Genes Dev |
| Abstract |
Alternative polyadenylation (APA) is widespread in neuronal development and activity-mediated neural plasticity. However, the underlying molecular mechanisms are largely unknown. We used systematic genetic studies and genome-wide surveys of the transcriptional landscape to identify a context-dependent regulatory pathway controlling APA in the Caenorhabditis elegans nervous system. Loss of function in ssup-72, a Ser5 phosphatase for the RNA polymerase II (Pol II) C-terminal domain (CTD), dampens transcription termination at a strong intronic polyadenylation site (PAS) in unc-44/ankyrin yet promotes termination at the weak intronic PAS of the MAP kinase dlk-1. A nuclear protein, SYDN-1, which regulates neuronal development, antagonizes the function of SSUP-72 and several nuclear polyadenylation factors. This regulatory pathway allows the production of a neuron-specific isoform of unc-44 and an inhibitory isoform of dlk-1. Dysregulation of the unc-44 and dlk-1 mRNA isoforms in sydn-1 mutants impairs neuronal development. Deleting the intronic PAS of unc-44 results in increased pre-mRNA processing of neuronal ankyrin and suppresses sydn-1 mutants. These results reveal a mechanism by which regulation of CTD phosphorylation controls coding region APA in the nervous system. |
| Volume | 29(22) |
| Pages | 2377-90 |
| Published | 2015-11-15 |
| DOI | 10.1101/gad.266650.115 |
| PII | 29/22/2377 |
| PMID | 26588990 |
| PMC | PMC4691892 |
| MeSH | Animals Ankyrins / genetics Ankyrins / metabolism Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Gene Expression Regulation, Developmental MAP Kinase Kinase Kinases / genetics MAP Kinase Kinase Kinases / metabolism Mutation Neurons / enzymology Phosphoprotein Phosphatases / genetics Phosphoprotein Phosphatases / metabolism* Polyadenylation Protein Binding |
| IF | 9.527 |
| Times Cited | 4 |
| WOS Category | DEVELOPMENTAL BIOLOGY GENETICS & HEREDITY CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 3 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm2304 tm349 tm2715 tm2802 tm2657 tm4024 |