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.
Please note: Abstract shown here should NOT be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
The Genetics Society of America
9650 Rockville Pike, Bethesda, MD
Phone: 301-634-7300, Fax: 301-634-7079
Questions and Comments: email@example.com