Tissue-specific regulation of alternative polyadenylation represses expression of a neuronal ankyrin isoform in C. elegans epidermal 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.

• Authors: Fei Chen, Andrew D Chisholm, Yishi Jin
• Journal: Development (Cambridge, England) (Development) Vol. 144 Issue 4 Pg. 698-707 (02 15 2017) ISSN: 1477-9129 [Electronic] England
• PMID: 28087624 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2017. Published by The Company of Biologists Ltd.

Chemical References

• Ankyrins
• Caenorhabditis elegans Proteins
• Protein Isoforms
• RNA, Messenger
• Green Fluorescent Proteins
• Death-Associated Protein Kinases

Topics

• Animals
• Ankyrins (genetics, 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