Zheng Dinghai, Tian Bin
Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, 185 South Orange Ave., Newark, NJ, 07103, USA.
Adv Exp Med Biol. 2014;825:97-127. doi: 10.1007/978-1-4939-1221-6_3.
Almost all eukaryotic pre-mRNAs are processed at the 3' end by the cleavage and polyadenylation (C/P) reaction, which preludes termination of transcription and gives rise to the poly(A) tail of mature mRNA. Genomic studies in recent years have indicated that most eukaryotic mRNA genes have multiple cleavage and polyadenylation sites (pAs), leading to alternative cleavage and polyadenylation (APA) products. APA isoforms generally differ in their 3' untranslated regions (3' UTRs), but can also have different coding sequences (CDSs). APA expands the repertoire of transcripts expressed from the genome, and is highly regulated under various physiological and pathological conditions. Growing lines of evidence have shown that RNA-binding proteins (RBPs) play important roles in regulation of APA. Some RBPs are part of the machinery for C/P; others influence pA choice through binding to adjacent regions. In this chapter, we review cis elements and trans factors involved in C/P, the significance of APA, and increasingly elucidated roles of RBPs in APA regulation. We also discuss analysis of APA using transcriptome-wide techniques as well as molecular biology approaches.
几乎所有真核生物的前体mRNA在3'端都要通过切割和聚腺苷酸化（C/P）反应进行加工，该反应是转录终止的前奏，并产生成熟mRNA的聚（A）尾。近年来的基因组研究表明，大多数真核生物mRNA基因具有多个切割和聚腺苷酸化位点（pA），从而产生可变切割和聚腺苷酸化（APA）产物。APA异构体通常在其3'非翻译区（3'UTR）有所不同，但也可能具有不同的编码序列（CDS）。APA扩展了基因组表达的转录本库，并在各种生理和病理条件下受到高度调控。越来越多的证据表明，RNA结合蛋白（RBP）在APA调控中发挥重要作用。一些RBP是C/P机制的一部分；其他RBP则通过与相邻区域结合来影响pA的选择。在本章中，我们综述了参与C/P的顺式元件和反式因子、APA的意义以及RBP在APA调控中日益明确的作用。我们还讨论了使用全转录组技术以及分子生物学方法对APA进行的分析。
