Presentation/Session Information

Session Information

Session Title: Neuronal Development Session Type: Parallel
Session Location: Grand Horizon Ballroom Session Time: Fri, Jun 26 8:30AM - 11:30AM

Presentation Information

Program Number: 86 Presentation Time: 8:30AM - 8:42AM

Presentation Content

Tuning of the RNA polymerase II CTD phosphatase SSUP-72 at internal poly(A) sites controls alternative polyadenylation in C. elegans neurons.Fei Chen 1,3, Yu Zhou 2, Yingchuan B. Qi 1, Vishal Khivansara 4, Hairi Li 2, Sang Young Chun 4, John K Kim 4, Xiang-Dong Fu 2, Yishi Jin 1,2,3. 1)Neurobiology section, University of California, San Diego, La Jolla, CA; 2)Dept. Cell. Mol. Med., University of California, San Diego, La Jolla, CA; 3)Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA; 4)Life Sciences Institute, University of Michigan, Ann Arbor, MI

Alternative polyadenylation (APA) plays important roles in generating transcriptome diversity under physiological and pathological conditions. However, the underlying molecular mechanisms are poorly understood. By using systematic genetic studies and genome-wide surveys of the transcriptional landscape in C. elegans, we identify an APA pathway that is required for neuron development. We show that SYDN-1, a novel nuclear protein (Van Epps et al, 2010), can antagonize SSUP-72, a Ser5 phosphatase for the RNA polymerase II (Pol II) Carboxyl-Terminal Domain (CTD), and controls the mRNA isoform production of two neuronal genes, unc-44/Ankryrin and dlk-1/MAPKKK. Exclusion of SSUP-72 activity at a strong internal poly(A) site (PAS) in unc-44 dampens its usage and allows the production of a neuron-specific ankyrin long isoform. Conversely, at the weak internal PAS of dlk-1, SSUP-72 exclusion promotes its usage and produces short isoform to control its activity. Dysregulation of unc-44 and dlk-1 mRNA isoforms impairs neuronal development. Our results demonstrate a mechanism by which tissue-specific and gene-specific APA is achieved via regulation of select internal PASs.




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