RRC ID 45535
著者 Chen F, Zhou Y, Qi YB, Khivansara V, Li H, Chun SY, Kim JK, Fu XD, Jin Y.
タイトル Context-dependent modulation of Pol II CTD phosphatase SSUP-72 regulates alternative polyadenylation in neuronal development.
ジャーナル 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.
巻・号 29(22)
ページ 2377-90
公開日 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
引用数 4
WOS 分野 DEVELOPMENTAL BIOLOGY GENETICS & HEREDITY CELL BIOLOGY
リソース情報
線虫 tm2304 tm349 tm2715 tm2802 tm2657 tm4024