RRC ID 53393
Author Chen F, Chisholm AD, Jin Y.
Title Tissue-specific regulation of alternative polyadenylation represses expression of a neuronal ankyrin isoform in C. elegans epidermal development.
Journal Development
Abstract Differential mRNA polyadenylation plays an important role in shaping the neuronal transcriptome. In C. elegans, several ankyrin isoforms are produced from the unc-44 locus 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 kinase dapk-1 We 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 of sydn-1 blocks ectopic expression of neuronal ankyrin and suppresses epidermal morphology defects of dapk-1 These effects of sydn-1 are mediated by ssup-72 autonomously 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 in dapk-1 mutants. Our data reveal that tissue and stage-specific expression of ankyrin isoforms relies on differential activity of positive and negative regulators of alternative polyadenylation.
Volume 144(4)
Pages 698-707
Published 2017-2-15
DOI 10.1242/dev.146001
PII dev.146001
PMID 28087624
PMC PMC5312038
MeSH Animals Ankyrins / genetics Ankyrins / metabolism* Caenorhabditis elegans / embryology* Caenorhabditis elegans Proteins / metabolism* Cell Nucleus / metabolism Death-Associated Protein Kinases / metabolism Epidermis / embryology* Gene Expression Profiling Gene Expression Regulation, Developmental* Green Fluorescent Proteins / metabolism Introns Mutation Neurons / metabolism* Phenotype Polyadenylation Protein Isoforms RNA, Messenger / metabolism Tissue Distribution
IF 5.611
Times Cited 5
C.elegans tm2304 tm349 tm2235