高通量测序技术在可选择性多聚腺苷酸化研究中的应用

Genome-wide alternative polyadenylation in animals:insights from high-throughput technologies

可选择性多聚腺苷酸化(alternative polyadenylation,APA)在基因表达调控中起着重要的作用。位于最后一个外显子的APA可以产生具有不同3'UTR长度的mRNA异构体,在细胞中可影响信使RNA(messager RNA,mRNA)的稳定性、翻译效率、转运及亚细胞定位等。随着第二代高通量测序技术的发展,研究人员近年来发展了许多高通量测序文库制备方法,对全基因组APA进行测序和分析。综述了当前研究全基因组水平APA的技术,并且总结了APA与一系列关键生物现象的关系,包括免疫应答、神经反应、胚胎发育和肿瘤发生等。随着APA研究的深入,APA越发成为新的基因转录与翻译调控的研究热点。

Alternative polyadenylation （APA） plays an important role in gene expression regulation network. APA located in the last exon can produce mRNA isoforms with 3＇UTRs of different length, which can impact the mRNA stability, translation efficiency, and subcellular translocation. However, the genome-wide APA events have been more systematically studied only recently with newly developed high-throughput methods. Here we reviewed the recent technological development of APA studies in a genome-wide scale. We also summarized the APA studies on several biological processes in animals including cancerous transformation, immune responses, embryonic development and neuron activity. With the highly enlarged scope of genome-wide APA analyses, function and mechanism of APA regulations have been increasingly become a new paradigm for the gene transcription network.