Formation, regulation and evolution of Caenorhabditis elegans 3'UTRs.
Formation, regulation and evolution of Caenorhabditis elegans 3'UTRs.
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DOI：
10.1038/nature09616
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发表时间：
2011-01-06
期刊：
影响因子：
64.8
通讯作者：
Bartel, David P.
中科院分区：
文献类型：
--
作者：
Jan, Calvin H.;Friedman, Robin C.;Ruby, J. Graham;Bartel, David P.
转录后基因调控通常通过mRNA 3′非翻译区（UTR）元件进行。尽管在秀丽隐杆线虫中发现了3 'UTR介导的基因调节的关键作用，但大多数秀丽隐杆线虫。线虫基因缺少注释的3′ UTR。在这里，我们描述了一种高通量的方法来可靠地识别多聚腺苷酸化的RNA末端，我们应用这种方法，称为聚（A）-位置分析测序（3 P-Seq），以确定C。elegans 3′ UTR.与最近也应用于C的标准方法相比。对于线虫UTR，3 P-Seq鉴定了8，581个额外的UTR，同时排除了数千个看起来不真实的较短UTR同种型。对这一扩展和校正数据集的分析表明，C.线虫3′ UTR促进了基因组的紧密化，因为富含A/U的切割和多聚腺苷酸化元件更容易出现在富含A/U的区域。事实上，30%的蛋白质编码基因的mRNA具有替代的、部分重叠的末端区域，这些区域产生另外10，498个切割和多聚腺苷酸化位点，这些位点基本上未被注意到，并代表了进行性UTR缩短的潜在进化中间体。此外，三分之一的会聚转录基因利用双向元件的回文排列来指定具有会聚重叠的UTR，这也通过消除基因之间的区域而有助于基因组压缩。虽然线虫3′ UTR的长度中位数仅为哺乳动物3′ UTR的六分之一，但它们的保守microRNA位点密度是哺乳动物的两倍，部分原因是其他类型的种子互补位点优先保守。这些发现揭示了切割和多聚腺苷酸化对基因组结构进化的影响，并为研究转录后基因调控提供了资源。
Posttranscriptional gene regulation frequently occurs through elements in mRNA 3′ untranslated regions (UTRs). Although crucial roles for 3′UTR-mediated gene regulation have been found in Caenorhabditis elegans, most C. elegans genes have lacked annotated 3′UTRs. Here we describe a high-throughput method to reliably identify polyadenylated RNA termini, and we apply this method, called poly(A)-position profiling by sequencing (3P-Seq), to determine C. elegans 3′UTRs. Compared to standard methods also recently applied to C. elegans UTRs, 3P-Seq identified 8,581 additional UTRs while excluding thousands of shorter UTR isoforms that do not appear to be authentic. Analysis of this expanded and corrected dataset suggested that the high A/U content of C. elegans 3′UTRs facilitated genome compaction, since the elements specifying cleavage and polyadenylation, which are A/U-rich, can more readily emerge in A/U rich regions. Indeed, 30% of the protein-coding genes have mRNAs with alternative, partially overlapping end regions that generate another 10,498 cleavage and polyadenylation sites that had gone largely unnoticed and represent potential evolutionary intermediates of progressive UTR shortening. Moreover, a third of the convergently transcribed genes utilize palindromic arrangements of bidirectional elements to specify UTRs with convergent overlap, which also contributes to genome compaction by eliminating regions between genes. Although nematode 3′UTRs have median length only one-sixth that of mammalian 3′UTRs, they have twice the density of conserved microRNA sites, in part because additional types of seed-complementary sites are preferentially conserved. These findings reveal the influence of cleavage and polyadenylation on the evolution of genome architecture and provide resources for studying posttranscriptional gene regulation.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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DOI：
10.1073/pnas.0900028106
发表时间：
2009-04-28
影响因子：
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作者：
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通讯作者：
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