前体mRNA的选择性多聚腺苷酸化与人类疾病  

Alternative Polyadenylation of Pre-mRNA and Related Human Diseases

作　　者：徐本锦 刘玲 XU Ben-Jin;LIU Ling(Laboratory Medicine Department in Fenyang College of Shanxi Medical University,Fenyang 032200,China)

机构地区：[1]山西医科大学汾阳学院医学检验系,汾阳032200

出　　处：《生物化学与生物物理进展》2020年第3期199-209,共11页Progress In Biochemistry and Biophysics

基　　金：山西医科大学汾阳学院引进人才启动金资助项目(2020A01)。

摘　　要：真核细胞的前体mRNA必须经过复杂的加工过程才能成熟,包括5’端加帽、剪接和3’端加工,其中3’加工包括3’端的切割和多聚腺苷酸化.该过程由前体mRNA上的顺式作用元件以及多个蛋白质因子控制.组成哺乳动物前体mRNA3’端加工机器的核心蛋白质复合体有切割和多聚腺苷酸化特异性因子、切割刺激因子、切割因子Ⅰ和切割因子Ⅱ.其他因子包括poly(A)聚合酶、poly(A)结合蛋白、偶对蛋白(symplekin)等.哺乳动物基因通常含有多个ploy(A)位点,选择性多聚腺苷酸化不仅可产生具有不同长度3’UTR的mRNA异构体,还可能改变基因的CDS区.作为真核生物基因表达调控的关键机制,选择性多聚腺苷酸化在细胞生长、增殖和分化中起着重要作用.本文综述了哺乳动物前体mRNA的3’端加工过程,3’端加工机器的组成及功能,探讨了选择性多聚腺苷酸化在多种人类疾病中的作用机制,以期为读者带来一些新的见解.The pre-mRNA of eukaryotic cells must undergo extensive and complex processes to produce mature mRNAs, including 5’ end capping, splicing and 3’ end processing. Among them, 3’ end processing includes cleavage and polyadenylation, which is controlled by the cis-elements of pre-mRNA and a number of protein factors. Mammalian 3’ end processing machinery consists of cleavage and polyadenylation factors, cleavage and stimulating factors, cleavage factor Ⅰ and cleavage factor Ⅱ. Other protein factors include poly(A) polymerase,poly(A) binding protein, symplekin and so on. Mammalian genes usually contain multiple polyadenylation sites,and alternative polyadenylation can not only produce mRNA variants with different length of 3’UTR, but also change the CDS region of genes. As a key mechanism for the regulation of gene expression in eukaryotes,alternative polyadenylation plays an important role in cell growth, proliferation and differentiation. This paper reviews the formation of the 3’ end of mammalian pre-mRNA, the composition and function of the 3’ end processing machinery, the mechanism of alternative polyadenylation in various human diseases, and hope to bring some new insights to readers.

关 键 词：多聚腺苷酸化 3’UTR 前体MRNA 选择性多聚腺苷酸化 人类疾病 

分 类 号：Q75[生物学—分子生物学]