Department Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Department Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
Molecules. 2021 May 11;26(10):2836. doi: 10.3390/molecules26102836.
The neuronal Hu/ELAV-like proteins HuB, HuC and HuD are a class of RNA-binding proteins that are crucial for proper development and maintenance of the nervous system. These proteins bind to AU-rich elements (AREs) in the untranslated regions (3'-UTRs) of target mRNAs regulating mRNA stability, transport and translation. In addition to these cytoplasmic functions, Hu proteins have been implicated in alternative splicing and alternative polyadenylation in the nucleus. The purpose of this study was to identify transcriptome-wide effects of HuD deletion on both of these nuclear events using RNA sequencing data obtained from the neocortex of (HuD KO) mice. HuD KO affected alternative splicing of 310 genes, including 17 validated HuD targets such as and . In addition, deletion of HuD affected polyadenylation of 53 genes, with the majority of significantly altered mRNAs shifting towards usage of proximal polyadenylation signals (PAS), resulting in shorter 3'-UTRs. None of these genes overlapped with those showing alternative splicing events. Overall, HuD KO had a greater effect on alternative splicing than polyadenylation, with many of the affected genes implicated in several neuronal functions and neuropsychiatric disorders.
神经元 Hu/ELAV 样蛋白 HuB、HuC 和 HuD 是一类 RNA 结合蛋白，对神经系统的正常发育和维持至关重要。这些蛋白质结合到靶 mRNA 的非翻译区（3'-UTR）中的富含 AU 的元件（AREs），调节 mRNA 的稳定性、运输和翻译。除了这些细胞质功能外，Hu 蛋白还参与核内的可变剪接和可变多聚腺苷酸化。本研究的目的是使用从 HuD KO 小鼠新皮层获得的 RNA 测序数据，鉴定 HuD 缺失对这两种核事件的转录组范围的影响。HuD KO 影响了 310 个基因的可变剪接，包括 17 个经验证的 HuD 靶基因，如 和 。此外，HuD 的缺失影响了 53 个基因的多聚腺苷酸化，大多数显著改变的 mRNA 倾向于使用近端多聚腺苷酸化信号（PAS），导致 3'-UTR 变短。这些基因中没有一个与显示可变剪接事件的基因重叠。总体而言，HuD KO 对可变剪接的影响大于多聚腺苷酸化，许多受影响的基因与几种神经元功能和神经精神疾病有关。
