Dynamic landscape of alternative polyadenylation during retinal development.
Dynamic landscape of alternative polyadenylation during retinal development.
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视网膜发育过程中替代多腺苷酸化的动态景观
DOI：
10.1007/s00018-016-2429-1
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Xiang M
中科院分区：
文献类型：
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作者：
Hu W;Li S;Park JY;Boppana S;Ni T;Li M;Zhu J;Tian B;Xie Z;Xiang M
中枢神经系统（CNS）的发育是一个复杂的过程，必须在多个水平上进行精细控制，以确保产生适当类型和数量的神经元。RNA选择性多聚腺苷酸化（阿帕）有助于转录组多样性和基因调控，最近已被证明在中枢神经系统中广泛存在。然而，以往的研究主要集中在阿帕的组织特异性和整个模式生物的发育阿帕的变化，阿帕的使用在中枢神经系统发育过程中缺乏系统的调查。在这里，我们在小鼠视网膜发育过程中对阿帕进行了全面分析，并确定了阶段特异性多聚腺苷酸化（PA）位点，这些位点富含对视网膜发育和视觉感知至关重要的基因。此外，我们证明了3′UTR（非翻译区）延长和内含子pA位点的使用增加，导致获得许多不同的RBP（RNA结合蛋白）和miRNA靶位点。此外，我们发现，相当数量的多聚腺苷酸化lncRNA与参与视网膜发育和功能的蛋白质编码基因共表达。总之，我们的数据表明，阿帕是高度和动态调节视网膜发育和成熟过程中，这表明阿帕可能作为一个重要的基因调控机制的微妙的过程中中枢神经系统的发展。
The development of the central nervous system (CNS) is a complex process that must be exquisitely controlled at multiple levels to ensure the production of appropriate types and quantity of neurons. RNA alternative polyadenylation (APA) contributes to transcriptome diversity and gene regulation, and has recently been shown to be widespread in the CNS. However, the previous studies have been primarily focused on the tissue specificity of APA and developmental APA change of whole model organisms; a systematic survey of APA usage is lacking during CNS development. Here, we conducted global analysis of APA during mouse retinal development, and identified stage-specific polyadenylation (pA) sites that are enriched for genes critical for retinal development and visual perception. Moreover, we demonstrated 3′UTR (untranslated region) lengthening and increased usage of intronic pA sites over development that would result in gaining many different RBP (RNA-binding protein) and miRNA target sites. Furthermore, we showed that a considerable number of polyadenylated lncRNAs are co-expressed with protein-coding genes involved in retinal development and functions. Together, our data indicate that APA is highly and dynamically regulated during retinal development and maturation, suggesting that APA may serve as a crucial mechanism of gene regulation underlying the delicate process of CNS development.