A novel mechanism of LIN-28 regulation of let-7 microRNA expression revealed by in vivo HITS-CLIP in C. elegans.
A novel mechanism of LIN-28 regulation of let-7 microRNA expression revealed by in vivo HITS-CLIP in C. elegans.
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DOI：
10.1261/rna.045542.114
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发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Slack FJ
中科院分区：
文献类型：
--
作者：
Stefani G;Chen X;Zhao H;Slack FJ
进化上保守的基因lin-28编码一种rna结合蛋白，是无脊椎动物和脊椎动物几种发育事件适当时间序列的重要调节因子。在细胞水平上，LIN-28促进细胞的干性和增殖，并抑制分化，当LIN-28与NANOG、OCT4和SOX2在人成纤维细胞中异位表达时，其诱导多能性的能力最能说明这一特征。哺乳动物的LIN28部分功能是通过let-7前远环区域的GGAG结合位点调节let-7 microRNA的加工。然而，许多人类和动物的let-7前体缺乏GGAG结合基序。为了剖析其在活体动物中生物学功能的分子机制，我们通过在秀丽隐杆线虫体内的HITS-CLIP鉴定了LIN-28与转录组相互作用的图谱。LIN-28结合了大量的信使rna，并且真正的LIN-28靶点的很大一部分涉及动物发育的各个方面。此外，我们的数据显示，LIN-28通过结合let-7 microRNA在一个未知区域的主要转录本来调节其表达，揭示了一种新的调控机制。
The evolutionarily conserved gene lin-28 encodes an RNA-binding protein and is an important regulator of the proper temporal succession of several developmental events in both invertebrates and vertebrates. At the cellular level, LIN-28 promotes stemness and proliferation, and inhibits differentiation, a feature best illustrated by its ability to induce pluripotency when ectopically expressed in human fibroblasts in combination with NANOG, OCT4, and SOX2. Mammalian LIN28 functions in part by regulating processing of the let-7 microRNA through a GGAG binding site in the pre-let-7’s distal loop region. However, many human and animal let-7 precursors lack the GGAG binding motif. In order to dissect the molecular mechanisms underlying its biological functions in a living animal, we identified a map of LIN-28 interactions with the transcriptome by in vivo HITS-CLIP in Caenorhabditis elegans. LIN-28 binds a large pool of messenger RNAs, and a substantial fraction of the bona fide LIN-28 targets are involved in aspects of animal development. Furthermore, our data show that LIN-28 regulates the expression of the let-7 microRNA by binding its primary transcript in a previously unknown region, revealing a novel regulatory mechanism.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
4.1
作者：
Graf R;Munschauer M;Mastrobuoni G;Mayr F;Heinemann U;Kempa S;Rajewsky N;Landthaler M
通讯作者：
Landthaler M
影响因子：
4.5
作者：
Hafner, Markus;Max, Klaas E. A.;Tuschl, Thomas
通讯作者：
Tuschl, Thomas
影响因子：
10.5
作者：
ARASU, P;WIGHTMAN, B;RUVKUN, G
通讯作者：
RUVKUN, G
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS