title: Tissue-specific regulation of alternative polyadenylation represses expression of a neuronal ankyrin isoform inC. elegansepidermal development.
abstract: Differential mRNA polyadenylation plays an important role in shaping the neuronal transcriptome. InC. elegans, several ankyrin isoforms are produced from theunc-44locus through alternative polyadenylation. Here, we identify a key role for an intronic polyadenylation site (PAS) in temporal- and tissue-specific regulation of UNC-44/ankyrin isoforms. Removing an intronic PAS results in ectopic expression of the neuronal ankyrin isoform in non-neural tissues. This mis-expression underlies epidermal developmental defects in mutants of the conserved tumor suppressor death-associated protein kinasedapk-1We have previously reported that the use of this intronic PAS depends on the nuclear polyadenylation factor SYDN-1, which inhibits the RNA polymerase II CTD phosphatase SSUP-72. Consistent with this, loss ofsydn-1blocks ectopic expression of neuronal ankyrin and suppresses epidermal morphology defects ofdapk-1These effects ofsydn-1are mediated byssup-72autonomously in the epidermis. We also show that a peptidyl-prolyl isomerase PINN-1 antagonizes SYDN-1 in the spatiotemporal control of neuronal ankyrin isoform. Moreover, the nuclear localization of PINN-1 is altered indapk-1mutants. Our data reveal that tissue and stage-specific expression of ankyrin isoforms relies on differential activity of positive and negative regulators of alternative polyadenylation.
authors.affiliation: Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.|Howard Hughes Medical Institute, Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Chisholm
authors.affiliation: Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA yijin@ucsd.edu.|Howard Hughes Medical Institute, Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Yishi
authors.identifier: 0000-0002-9371-9860
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D064550:Death-Associated Protein Kinases / Q000378:metabolism; D004817:Epidermis / Q000196:embryology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007438:Introns; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype; D026723:Polyadenylation; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D017487:Ankyrins; D029742:Caenorhabditis elegans Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D064550:Death-Associated Protein Kinases
keywords: DAPK-1/DAP kinase; Nuclear polyadenylation; PINN-1/PIN1 peptidyl-prolyl isomerase; SSUP-72/SSU72; SYDN-1