Differential repression of alternative transcripts: a screen for miRNA targets.
Differential repression of alternative transcripts: a screen for miRNA targets.
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替代转录本的差异抑制：miRNA靶标的屏幕。
DOI：
10.1371/journal.pcbi.0020043
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发表时间：
2006-05
影响因子：
4.3
通讯作者：
Gautheret, Daniel
中科院分区：
文献类型：
--
作者：
Legendre, Matthieu;Ritchie, William;Lopez, Fabrice;Gautheret, Daniel
不同的多聚腺苷酸化位点产生具有不同长度的3‘非翻译区(UTRs)的转录物异构体。如果在非编码区中存在microRNA(MiRNA)靶标，那么只有那些含有靶标的异构体才对同源miRNA的控制敏感。我们对包含多个聚(A)位点和可能的miRNA靶标的3‘UTRs进行了系统的研究。基于表达序列标签(EST)计数和EST文库信息，我们观察到，在表达相应miRNA的组织中，包含miR-1或miR-124靶标的异构体水平降低。对3‘UTRs中所有保守的7-MERS重复了这一分析，得到了312个基序。我们表明，这一组显著富含已知的miRNA靶标和mRNA不稳定元件，这验证了我们最初的假设。我们扫描了人类基因组中可能的同源miRNAs，并确定了与我们的基序匹配的在系统发育上保守的前体。这种分析可以帮助识别在以前的筛查中没有发现的靶-miRNA对，但它也可能揭示其他类型调控因素的靶标。MicroRNAs(MiRNAs)是识别mRNAs 3‘区特定靶序列的短RNA分子。然后，这些miRNAs可以特异性地阻止mRNAs被表达或翻译成蛋白质。在这篇文章中，作者询问了当靶向mRNA具有不同于其3‘区的几种形式时会发生什么。这种3‘端变异是很常见的。如果在同一个mRNA中存在两个或两个以上的变异，结果是两个或更多具有不同长度的3‘端的mRNAs。如果miRNA靶标位于两个可变点之间，则较短的转录本应该是无靶标的，应该逃脱miRNA介导的抑制，而较长的转录本应该被抑制。为了验证这一假设，作者观察了具有这些变量3‘端的mRNAs。含有特定miRNAs靶标的变体在发现这些特定miRNAs的组织中似乎特别表达不足。利用这一原理在3‘区中寻找具有类似效果的其他序列模式，并获得312个显著模式的列表。然后，作者扫描了基因组序列，并确定了这些模式可能的同源miRNAs。这一新知识将有助于进一步了解基因是如何控制的。
Alternative polyadenylation sites produce transcript isoforms with 3′ untranslated regions (UTRs) of different lengths. If a microRNA (miRNA) target is present in the UTR, then only those target-containing isoforms should be sensitive to control by a cognate miRNA. We carried out a systematic examination of 3′ UTRs containing multiple poly(A) sites and putative miRNA targets. Based on expressed sequence tag (EST) counts and EST library information, we observed that levels of isoforms containing targets for miR-1 or miR-124, two miRNAs causing downregulation of transcript levels, were reduced in tissues expressing the corresponding miRNA. This analysis was repeated for all conserved 7-mers in 3′ UTRs, resulting in a selection of 312 motifs. We show that this set is significantly enriched in known miRNA targets and mRNA-destabilizing elements, which validates our initial hypothesis. We scanned the human genome for possible cognate miRNAs and identified phylogenetically conserved precursors matching our motifs. This analysis can help identify target-miRNA couples that went undetected in previous screens, but it may also reveal targets for other types of regulatory factors. MicroRNAs (miRNAs) are short RNA molecules that recognize specific target sequences in the 3′ region of mRNAs. These miRNAs can then specifically keep the mRNAs from being expressed, or translated into proteins. In this article, the authors ask what happens when a targeted mRNA has several forms differing by their 3′ regions. Such 3′ variations are very common. If two or more variations are present in a single mRNA, the result is two or more mRNAs with 3′ ends of different lengths. If an miRNA target is located between the two sites of variability, the shorter transcript should be target free and should escape miRNA-mediated inhibition, while longer transcripts should be inhibited. To test this hypothesis, the authors looked at mRNAs that had these variable 3′ ends. Variants containing targets for certain miRNAs appeared to be specifically underrepresented in tissues where these particular miRNAs are found. This principle was used to find other sequence patterns in 3′ regions that had a similar effect, and a list of 312 significant patterns was obtained. The authors then scanned genome sequences and identified possible cognate miRNAs for these patterns. This new knowledge will help further an understanding of how genes are controlled.
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影响因子：
9.8
作者：
Imanishi T;Itoh T;Suzuki Y;O'Donovan C;Fukuchi S;Koyanagi KO;Barrero RA;Tamura T;Yamaguchi-Kabata Y;Tanino M;Yura K;Miyazaki S;Ikeo K;Homma K;Kasprzyk A;Nishikawa T;Hirakawa M;Thierry-Mieg J;Thierry-Mieg D;Ashurst J;Jia L;Nakao M;Thomas MA;Mulder N;Karavidopoulou Y;Jin L;Kim S;Yasuda T;Lenhard B;Eveno E;Suzuki Y;Yamasaki C;Takeda J;Gough C;Hilton P;Fujii Y;Sakai H;Tanaka S;Amid C;Bellgard M;Bonaldo Mde F;Bono H;Bromberg SK;Brookes AJ;Bruford E;Carninci P;Chelala C;Couillault C;de Souza SJ;Debily MA;Devignes MD;Dubchak I;Endo T;Estreicher A;Eyras E;Fukami-Kobayashi K;Gopinath GR;Graudens E;Hahn Y;Han M;Han ZG;Hanada K;Hanaoka H;Harada E;Hashimoto K;Hinz U;Hirai M;Hishiki T;Hopkinson I;Imbeaud S;Inoko H;Kanapin A;Kaneko Y;Kasukawa T;Kelso J;Kersey P;Kikuno R;Kimura K;Korn B;Kuryshev V;Makalowska I;Makino T;Mano S;Mariage-Samson R;Mashima J;Matsuda H;Mewes HW;Minoshima S;Nagai K;Nagasaki H;Nagata N;Nigam R;Ogasawara O;Ohara O;Ohtsubo M;Okada N;Okido T;Oota S;Ota M;Ota T;Otsuki T;Piatier-Tonneau D;Poustka A;Ren SX;Saitou N;Sakai K;Sakamoto S;Sakate R;Schupp I;Servant F;Sherry S;Shiba R;Shimizu N;Shimoyama M;Simpson AJ;Soares B;Steward C;Suwa M;Suzuki M;Takahashi A;Tamiya G;Tanaka H;Taylor T;Terwilliger JD;Unneberg P;Veeramachaneni V;Watanabe S;Wilming L;Yasuda N;Yoo HS;Stodolsky M;Makalowski W;Go M;Nakai K;Takagi T;Kanehisa M;Sakaki Y;Quackenbush J;Okazaki Y;Hayashizaki Y;Hide W;Chakraborty R;Nishikawa K;Sugawara H;Tateno Y;Chen Z;Oishi M;Tonellato P;Apweiler R;Okubo K;Wagner L;Wiemann S;Strausberg RL;Isogai T;Auffray C;Nomura N;Gojobori T;Sugano S
通讯作者：
Sugano S
影响因子：
14.9
作者：
Tian B;Hu J;Zhang H;Lutz CS
通讯作者：
Lutz CS
影响因子：
14.9
作者：
DURET, L;DORKELD, F;GAUTIER, C
通讯作者：
GAUTIER, C
影响因子：
7
作者：
Gautheret, D;Poirot, O;Claverie, JM
通讯作者：
Claverie, JM
影响因子：
14.9
作者：
Griffiths-Jones, S
通讯作者：
Griffiths-Jones, S