Lee Seungjae, Aubee Joseph I, Lai Eric C
Developmental Biology Program, Sloan Kettering Institute, New York, NY, USA.
Developmental Biology Program, Sloan Kettering Institute, New York, NY, USA
Life Sci Alliance. 2023 Oct 4;6(12). doi: 10.26508/lsa.202302000. Print 2023 Dec.
Cell-type-specific gene expression is a fundamental feature of multicellular organisms and is achieved by combinations of regulatory strategies. Although cell-restricted transcription is perhaps the most widely studied mechanism, co-transcriptional and post-transcriptional processes are also central to the spatiotemporal control of gene functions. One general category of expression control involves the generation of multiple transcript isoforms from an individual gene, whose balance and cell specificity are frequently tightly regulated via diverse strategies. The nervous system makes particularly extensive use of cell-specific isoforms, specializing the neural function of genes that are expressed more broadly. Here, we review regulatory strategies and RNA-binding proteins that direct neural-specific isoform processing. These include various classes of alternative splicing and alternative polyadenylation events, both of which broadly diversify the neural transcriptome. Importantly, global alterations of splicing and alternative polyadenylation are characteristic of many neural pathologies, and recent genetic studies demonstrate how misregulation of individual neural isoforms can directly cause mutant phenotypes.
细胞类型特异性基因表达是多细胞生物的一个基本特征，它通过多种调控策略的组合来实现。尽管细胞限制性转录可能是研究最为广泛的机制，但共转录和转录后过程对于基因功能的时空控制也至关重要。一类普遍的表达控制涉及从单个基因产生多种转录本异构体，其平衡和细胞特异性经常通过多种策略受到严格调控。神经系统特别广泛地利用细胞特异性异构体，使更广泛表达的基因具有神经功能特异性。在这里，我们综述了指导神经特异性异构体加工的调控策略和RNA结合蛋白。这些包括各类可变剪接和可变聚腺苷酸化事件，这两者都广泛地使神经转录组多样化。重要的是，剪接和可变聚腺苷酸化的全局改变是许多神经病理学的特征，最近的遗传学研究表明单个神经异构体的调控异常如何直接导致突变表型。
