Miura Pedro, Sanfilippo Piero, Shenker Sol, Lai Eric C
Department of Developmental Biology, Sloan-Kettering Institute, New York, NY, USA.
Bioessays. 2014 Aug;36(8):766-77. doi: 10.1002/bies.201300174. Epub 2014 Jun 5.
Alternative cleavage and polyadenylation (APA) can diversify coding and non-coding regions, but has particular impact on increasing 3' UTR diversity. Through the gain or loss of regulatory elements such as RNA binding protein and microRNA sites, APA can influence transcript stability, localization, and translational efficiency. Strikingly, the central nervous systems of invertebrate and vertebrate species express a broad range of transcript isoforms bearing extended 3' UTRs. The molecular mechanism that permits proximal 3' end bypass in neurons is mysterious, and only beginning to be elucidated. This landscape of neural 3' UTR extensions, many reaching unprecedented lengths, may help service the unique post-transcriptional regulatory needs of neurons. A combination of approaches, including transcriptome-wide profiling, genetic screening to identify APA factors, biochemical dissection of alternative 3' end formation, and manipulation of individual neural APA targets, will be necessary to gain fuller perspectives on the mechanism and biology of neural-specific 3' UTR lengthening.
可变剪接和多聚腺苷酸化（APA）能够使编码区和非编码区多样化，但对增加3'UTR多样性有特别的影响。通过获得或失去诸如RNA结合蛋白和微小RNA位点等调控元件，APA可以影响转录本的稳定性、定位和翻译效率。引人注目的是，无脊椎动物和脊椎动物物种的中枢神经系统表达了广泛的具有延长3'UTR的转录本异构体。允许神经元近端3'端绕过的分子机制尚不清楚，才刚刚开始被阐明。这种神经3'UTR延长的情况，许多达到了前所未有的长度，可能有助于满足神经元独特的转录后调控需求。需要综合多种方法，包括全转录组分析、基因筛选以鉴定APA因子、对可变3'端形成进行生化剖析以及对单个神经APA靶点进行操作，以便更全面地了解神经特异性3'UTR延长的机制和生物学特性。
