Context-dependent modulation of Pol II CTD phosphatase SSUP-72 regulates alternative polyadenylation in neuronal development
作者： Fei Chen , Yu Zhou , Yingchuan B. Qi , Vishal Khivansara , Hairi Li
关键词: Gene isoform 、 Phosphorylation 、 Polyadenylation 、 Biology 、 Genetics 、 Regulatory Pathway 、 Nuclear protein 、 Ankyrin 、 RNA polymerase II 、 MAP kinase kinase kinase
摘要: 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 genome-wide surveys of transcriptional landscape to identify a context-dependent regulatory pathway controlling APA Caenorhabditis elegans nervous system. Loss function ssup-72, Ser5 phosphatase for RNA polymerase II (Pol II) C-terminal domain (CTD), dampens transcription termination at strong intronic site (PAS) unc-44/ankyrin yet promotes weak PAS MAP kinase dlk-1. A nuclear protein, SYDN-1, which regulates development, antagonizes SSUP-72 several factors. This allows production neuron-specific isoform unc-44 an inhibitory Dysregulation dlk-1 mRNA isoforms sydn-1 mutants impairs development. Deleting results increased pre-mRNA processing ankyrin suppresses mutants. These reveal mechanism by regulation CTD phosphorylation controls coding region
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