Phylogenetic analysis of mRNA polyadenylation sites reveals a role of transposable elements in evolution of the 3'-end of genes.
Phylogenetic analysis of mRNA polyadenylation sites reveals a role of transposable elements in evolution of the 3'-end of genes.
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DOI：
10.1093/nar/gkn540
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发表时间：
2008-10
影响因子：
14.9
通讯作者：
Tian B
中科院分区：
文献类型：
--
作者：
Lee JY;Ji Z;Tian B
mRNA 多腺苷酸化是几乎所有真核 mRNA 成熟的重要步骤，并且与定义基因 3' 末端的转录终止紧密相关。大量人类和小鼠基因含有替代的聚腺苷酸化位点 [poly(A) 位点]，这些位点会导致包含不同 3' 非翻译区 (UTR) 和/或编码不同蛋白质序列的 mRNA 变体。在这里，我们研究了人类、小鼠、大鼠和鸡中不同类型的替代性 Poly(A) 位点的保守性和差异。我们发现 3' 最外显子的 Poly(A) 位点往往比上游位点更加保守，而位于 3' 最外显子上游的 Poly(A) 位点（也称为内含子 Poly(A) 位点）往往保守性要低得多。具有较长进化历史的基因更有可能具有替代多聚腺苷酸化，这表明通过进化获得了多聚（A）位点。我们还发现，非保守的 Poly(A) 位点与转座元件 (TE) 的关联程度比保守的位点高得多，尽管使用频率较低。不同类别的 TE 通过将 TE 序列扩展为聚腺苷酸化元件而与 Poly(A) 位点关联，从而具有不同的特征。我们的结果在几种脊椎动物中建立了替代性poly(A)位点的保守模式，并表明基因的3'端可以通过进化被TE动态修饰。
mRNA polyadenylation is an essential step for the maturation of almost all eukaryotic mRNAs, and is tightly coupled with termination of transcription in defining the 3′-end of genes. Large numbers of human and mouse genes harbor alternative polyadenylation sites [poly(A) sites] that lead to mRNA variants containing different 3′-untranslated regions (UTRs) and/or encoding distinct protein sequences. Here, we examined the conservation and divergence of different types of alternative poly(A) sites across human, mouse, rat and chicken. We found that the 3′-most poly(A) sites tend to be more conserved than upstream ones, whereas poly(A) sites located upstream of the 3′-most exon, also termed intronic poly(A) sites, tend to be much less conserved. Genes with longer evolutionary history are more likely to have alternative polyadenylation, suggesting gain of poly(A) sites through evolution. We also found that nonconserved poly(A) sites are associated with transposable elements (TEs) to a much greater extent than conserved ones, albeit less frequently utilized. Different classes of TEs have different characteristics in their association with poly(A) sites via exaptation of TE sequences into polyadenylation elements. Our results establish a conservation pattern for alternative poly(A) sites in several vertebrate species, and indicate that the 3′-end of genes can be dynamically modified by TEs through evolution.
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影响因子：
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