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.
The authors declare no competing or financial interests.
F.C., A.D.C. and Y.J. designed the study; F.C. performed experiments and analyzed the data; A.D.C. and Y.J. interpreted the data; F.C., A.D.C. and Y.J. wrote the manuscript.
This research was supported by the National Institutes of Health (R01 GM054657 to A.D.C. and R01 NS035546 to Y.J.). F.C. is an Associate of and Y.J. is an Investigator of the Howard Hughes Medical Institute. Deposited in PMC for release after 6 months.
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.146001.supplemental
- Received October 23, 2016.
- Accepted January 2, 2017.