A large-scale analysis of mRNA polyadenylation of human and mouse genes.

A large-scale analysis of mRNA polyadenylation of human and mouse genes.
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DOI:
10.1093/nar/gki158
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发表时间:
2005
影响因子:
14.9
通讯作者:
Lutz CS
Lutz CS
中科院分区:
生物学2区
文献类型:
--
作者:
Tian B;Hu J;Zhang H;Lutz CS

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信使核糖核酸化是真核生物中一个重要的细胞过程。它涉及新生mRNAs的3‘端切割和Poly(A)尾巴的添加,在mRNA的细胞代谢的许多方面发挥着重要作用。这一过程受切割位点周围的各种顺式作用元件及其结合因子的控制。在这项研究中,我们调查了13 942个人类基因和11 155个小鼠基因的包含切割位点的基因组区域[这里称为聚(A)位点]。我们发现,很大比例的人类和小鼠基因具有交替的多聚腺苷(∼分别为54%和32%)。在人类和小鼠的同源基因之间,交替的多聚腺苷酸化类型或多聚腺苷酸化构型的保守性具有统计学意义,这表明这两个物种广泛地利用交替的多腺苷酸化来产生替代的基因转录本。属于几个功能基团的基因,由它们的基因本体论注释表明,在多腺苷构型方面是有偏见的。许多Poly(A)位点含有多个切割位点(51.25%的人和46.97%的小鼠),导致转录本的3‘末端形成不均一。这意味着聚腺苷酸化的切割过程在很大程度上是不精确的。不同类型的聚(A)位点,就它们在基因中的相对位置而言,被发现在周围基因组区域具有不同的核苷酸组成。这项大规模的研究为哺乳动物物种中多聚腺苷酸化的机制提供了重要的见解,并代表了通过交替多聚腺苷酸化来调节基因表达的基因组观点。
mRNA polyadenylation is a critical cellular process in eukaryotes. It involves 3′ end cleavage of nascent mRNAs and addition of the poly(A) tail, which plays important roles in many aspects of the cellular metabolism of mRNA. The process is controlled by various cis-acting elements surrounding the cleavage site, and their binding factors. In this study, we surveyed genome regions containing cleavage sites [herein called poly(A) sites], for 13 942 human and 11 155 mouse genes. We found that a great proportion of human and mouse genes have alternative polyadenylation (∼54 and 32%, respectively). The conservation of alternative polyadenylation type or polyadenylation configuration between human and mouse orthologs is statistically significant, indicating that alternative polyadenylation is widely employed by these two species to produce alternative gene transcripts. Genes belonging to several functional groups, indicated by their Gene Ontology annotations, are biased with respect to polyadenylation configuration. Many poly(A) sites harbor multiple cleavage sites (51.25% human and 46.97% mouse sites), leading to heterogeneous 3′ end formation for transcripts. This implies that the cleavage process of polyadenylation is largely imprecise. Different types of poly(A) sites, with regard to their relative locations in a gene, are found to have distinct nucleotide composition in surrounding genomic regions. This large-scale study provides important insights into the mechanism of polyadenylation in mammalian species and represents a genomic view of the regulation of gene expression by alternative polyadenylation.
DOI: 10.1093/nar/30.8.1842
发表时间: 2002-04-15
影响因子: 14.9
作者:
Arhin, GK;Boots, M;Wilusz, J
通讯作者: Wilusz, J
DOI: 10.1101/gad.13.14.1884
发表时间: 1999-07-15
影响因子: 10.5
作者:
Loflin, P;Chen, CYA;Shyu, AB
通讯作者: Shyu, AB
DOI: 10.1093/nar/26.12.2891
发表时间: 1998-06-15
影响因子: 14.9
作者:
Chen, F;Wilusz, J
通讯作者: Wilusz, J
DOI: 10.1101/gr.190501
发表时间: 2001-09-01
期刊: GENOME RESEARCH
影响因子: 7
作者:
Beaudoing, E;Gautheret, D
通讯作者: Gautheret, D
DOI: 10.1016/s0303-7207(02)00044-8
发表时间: 2002-04-25
影响因子: 4.1
作者:
MacDonald, CC;Redondo, JL
通讯作者: Redondo, JL