Tissue-specific regulation of alternative polyadenylation represses expression of a neuronal ankyrin isoform in C. elegans epidermal development
Tissue-specific regulation of alternative polyadenylation represses expression of a neuronal ankyrin isoform in C. elegans epidermal development
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DOI：
10.1242/dev.146001
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发表时间：
2017-02-15
期刊：
影响因子：
4.6
通讯作者：
Jin, Yishi
中科院分区：
文献类型：
--
作者：
Chen, Fei;Chisholm, Andrew D.;Jin, Yishi
差异mRNA聚腺苷酸化在形成神经元转录组中起重要作用。In C.在线虫中，通过选择性多腺苷酸化从UNC-44基因座产生几种锚蛋白同种型。在这里，我们确定了一个关键作用的内含子多聚腺苷酸化位点（PAS）的时间和组织特异性调节的α-44/锚蛋白亚型。去除内含子PAS导致非神经组织中神经元锚蛋白同种型的异位表达。这种错误表达是保守的肿瘤抑制死亡相关蛋白激酶dapk-1突变体表皮发育缺陷的基础。我们以前曾报道，使用这种内含子PAS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，sydn-1的缺失阻断了神经元锚蛋白的异位表达，并抑制了dapk-1的表皮形态缺陷。sydn-1的这些作用由表皮中的ssup-72自主介导。我们还表明，肽基脯氨酰异构酶PINN-1拮抗SYDN-1在神经元锚蛋白亚型的时空控制。此外，PINN-1的核定位在dapk-1突变体中改变。我们的数据显示，锚蛋白亚型的组织和阶段特异性表达依赖于交替多聚腺苷酸化的阳性和阴性调节剂的差异活性。
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.