BioProject

Alternative polyadenylation (APA) plays important roles in generating transcriptomediversity. More...

Alternative polyadenylation (APA) plays important roles in generating transcriptomediversity. In the nervous system widespread APA are observed in development and activity-mediated neural plasticity. However, the underlying molecular mechanisms are largely unknown. Through systematic genetic studies and genome-wide survey of transcriptional landscape, here, we report a mechanism controlling APA of two neuronal genes, UNC-44/Ankyrin and DLK-1/MAPKK, during development of C. elegans nervous system. We show that SSUP-72, a Ser5 phosphatase for RNA polymerase II (Pol II) Carboxyl-Terminal Domain (CTD), differentially affects the usage of poly(A) sites (PASs) in the coding regions of unc-44 and dlk-1. A novel nuclear protein SYDN-1 interacts with both SSUP-72 and RNA pol II, and inhibits the function of SSUP-72 and nuclear polyadenylation factors. This regulatory pathway dampens the usage of a strong internal PAS of unc-44 for the production of neuron-specific ankyrin, and promotes the usage of a weak PAS of dlk-1 to control its activity. Deregulation of unc-44 and dlk-1 mRNA isoforms impairs neuronal development. Our data illustrate the high degree selectivity of APA regulation in complex nervous systems. Overall design: Two (2) wildtype N2 libraries and two (2) sydn-1 mutant libraries. Less...