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Formation, regulation and evolution of Caenorhabditis elegans 3'UTRs

机译:秀丽隐杆线虫3'UTRs的形成,调控和进化

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摘要

Post-transcriptional 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 for reliable identification of 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 iden-tified 8,580 additional UTRs while excluding thousands of shorter UTR isoforms that do not seem to be authentic. Analysis of this expanded and corrected data set suggested that the high A/U con-tent of C. elegans 3'UTRs facilitated genome compaction, because 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 10,480 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 use 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 con-served 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 evolu-tion of genome architecture and provide resources for studying post-transcriptional gene regulation.
机译:转录后基因调节经常通过mRNA 3'非翻译区(UTR)中的元件发生。尽管在秀丽隐杆线虫中发现了3'UTR介导的基因调控的关键作用,但是大多数秀丽隐杆线虫基因缺少注释的3'UTR。在这里,我们描述了一种高通量方法,用于可靠地鉴定聚腺苷酸化的RNA末端,并且我们将此方法称为通过测序(3P-Seq)进行的poly(A)位置分析,以确定秀丽隐杆线虫3'UTR。与最近也用于秀丽隐杆线虫UTR的标准方法相比,3P-Seq鉴定了8,580个额外的UTR,同时排除了数千个看起来不太真实的较短的UTR亚型。对这个扩展和校正后的数据集的分析表明,秀丽隐杆线虫3'UTR的高A / U含量促进了基因组紧缩,因为富含裂解液(A / U)的裂解和聚腺苷酸化元素可以更容易地在A中出现。 / U富裕的地区。确实,有30%的蛋白质编码基因的mRNA带有交替的,部分重叠的末端区域,这些末端区域会产生另外10,480个切割和聚腺苷酸化位点,这些位点在很大程度上并未引起人们的注意,并代表了逐步UTR缩短的潜在进化中间体。此外,三分之一的聚合转录基因使用双向元素的回文排列来指定具有聚合重叠的UTR,这也通过消除基因之间的区域而有助于基因组紧缩。尽管线虫3'UTR的中位长度仅为哺乳动物3'UTR的六分之一,但它们的密度是保守的microRNA位点的两倍,部分原因是优先保留了其他类型的种子互补位点。这些发现揭示了切割和聚腺苷酸化对基因组结构发展的影响,并为研究转录后基因调控提供了资源。

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  • 来源
    《Nature》 |2011年第7328期|p.97-101|共5页
  • 作者单位

    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA,Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA,Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA,Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA,Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA,Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California 94158, USA;

    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA,Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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