Chen Fei, Chisholm Andrew D, Jin Yishi
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.
Development. 2017 Feb 15;144(4):698-707. doi: 10.1242/dev.146001. Epub 2017 Jan 13.
Differential mRNA polyadenylation plays an important role in shaping the neuronal transcriptome. In , several ankyrin isoforms are produced from the 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 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 blocks ectopic expression of neuronal ankyrin and suppresses epidermal morphology defects of These effects of are mediated by 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 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.
差异性mRNA聚腺苷酸化在塑造神经元转录组中起重要作用。在[具体研究中]，通过可变聚腺苷酸化从[基因座]产生了几种锚蛋白亚型。在这里，我们确定了一个内含子聚腺苷酸化位点（PAS）在UNC-44/锚蛋白亚型的时间和组织特异性调控中的关键作用。去除一个内含子PAS会导致神经元锚蛋白亚型在非神经组织中异位表达。这种错误表达是保守的肿瘤抑制因子死亡相关蛋白激酶突变体中表皮发育缺陷的基础。我们之前报道过，这个内含子PAS的使用依赖于核聚腺苷酸化因子SYDN-1，它抑制RNA聚合酶II CTD磷酸酶SSUP-72。与此一致，[基因]缺失会阻止神经元锚蛋白的异位表达，并抑制[相关基因]突变体的表皮形态缺陷。[基因]的这些作用是由其在表皮中自主介导的。我们还表明，肽基脯氨酰异构酶PINN-1在神经元锚蛋白亚型的时空控制中拮抗SYDN-1。此外，PINN-1的核定位在[相关基因]突变体中发生改变。我们的数据表明，锚蛋白亚型的组织和阶段特异性表达依赖于可变聚腺苷酸化正负调节因子的差异活性。
