Alternative polyadenylation in the nervous system: to what lengths will 3' UTR extensions take us?
Alternative polyadenylation in the nervous system: to what lengths will 3' UTR extensions take us?
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DOI：
10.1002/bies.201300174
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Lai EC
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文献类型：
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作者：
Miura P;Sanfilippo P;Shenker S;Lai EC
交替切割和多聚腺苷酸化(APA)可以使编码区和非编码区多样化，但对增加3‘非编码区的多样性有特别的影响。APA通过RNA结合蛋白和microRNA位点等调控元件的获得或丢失，影响转录的稳定性、定位和翻译效率。值得注意的是，无脊椎动物和脊椎动物的中枢神经系统表达广泛的转录异构体，带有延伸的3‘UTRs。允许神经元近端3‘端旁路的分子机制是神秘的，而且只是刚刚开始被阐明。这种神经3‘非编码区延伸的图景，其中许多达到了前所未有的长度，可能有助于服务于神经元独特的转录后调控需求。为了更全面地了解神经特异性3‘UTR延长的机制和生物学，需要结合多种方法，包括转录组范围的图谱、识别APA因子的遗传筛选、替代3’端形成的生化解剖以及单个神经性APA靶标的操纵。
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.