Extensive microRNA-mediated crosstalk between lncRNAs and mRNAs in mouse embryonic stem cells.
Extensive microRNA-mediated crosstalk between lncRNAs and mRNAs in mouse embryonic stem cells.
复制标题
DOI：
10.1101/gr.181974.114
复制
发表时间：
2015-05
期刊：
影响因子：
7
通讯作者：
Marques AC
中科院分区：
文献类型：
--
作者：
Tan JY;Sirey T;Honti F;Graham B;Piovesan A;Merkenschlager M;Webber C;Ponting CP;Marques AC
最近，一些基因间长非编码 RNA (lncRNA) 已被证明与 mRNA 竞争与 miRNA 的结合，并导致发育和疾病。除了这些报道之外，我们对 lncRNA 介导的 miRNA 介导的 mRNA 水平调节的程度和功能后果知之甚少。为了进一步了解 lncRNA-mRNA miRNA 介导的串扰，我们重新分析了小鼠胚胎干细胞 (mESC) 中 100 多个 lncRNA 转录本的靶向敲低所引起的转录组范围的变化。我们预测，平均而言，lncRNA 诱导的转录水平变化中近五分之一依赖于 mESC 中高度丰富的 miRNA。我们通过暂时分析 mESC 中 miRNA 生物合成丧失后转录组范围内基因表达的变化，通过实验验证了这些发现。在 miRNA 耗尽后，我们发现超过 50% 的 lncRNA 及其依赖于 miRNA 的 mRNA 靶标协同上调，这与它们介导的相互作用一致。这些lncRNA优先位于细胞质中，并且它们与其靶标共享的miRNA的反应元件已通过纯化选择保留在哺乳动物中。最后，每个 lncRNA 的 miRNA 依赖性 mRNA 靶标往往具有共同的生物学功能。因此，在 mESC 中，转录后 miRNA 介导的 lncRNA 和 mRNA 之间的串扰令人惊讶地普遍存在，在哺乳动物中是保守的，并且可能有助于关键的发育过程。
Recently, a handful of intergenic long noncoding RNAs (lncRNAs) have been shown to compete with mRNAs for binding to miRNAs and to contribute to development and disease. Beyond these reports, little is yet known of the extent and functional consequences of miRNA-mediated regulation of mRNA levels by lncRNAs. To gain further insight into lncRNA-mRNA miRNA-mediated crosstalk, we reanalyzed transcriptome-wide changes induced by the targeted knockdown of over 100 lncRNA transcripts in mouse embryonic stem cells (mESCs). We predicted that, on average, almost one-fifth of the transcript level changes induced by lncRNAs are dependent on miRNAs that are highly abundant in mESCs. We validated these findings experimentally by temporally profiling transcriptome-wide changes in gene expression following the loss of miRNA biogenesis in mESCs. Following the depletion of miRNAs, we found that >50% of lncRNAs and their miRNA-dependent mRNA targets were up-regulated coordinately, consistent with their interaction being miRNA-mediated. These lncRNAs are preferentially located in the cytoplasm, and the response elements for miRNAs they share with their targets have been preserved in mammals by purifying selection. Lastly, miRNA-dependent mRNA targets of each lncRNA tended to share common biological functions. Post-transcriptional miRNA-mediated crosstalk between lncRNAs and mRNA, in mESCs, is thus surprisingly prevalent, conserved in mammals, and likely to contribute to critical developmental processes.
登录
查看更多内容
影响因子：
16
作者：
Bosson, Andrew D.;Zamudio, Jesse R.;Sharp, Phillip A.
通讯作者：
Sharp, Phillip A.
影响因子：
2.7
作者：
Fan M;Li X;Jiang W;Huang Y;Li J;Wang Z
通讯作者：
Wang Z
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
影响因子：
48
作者：
Ebert, Margaret S.;Neilson, Joel R.;Sharp, Phillip A.
通讯作者：
Sharp, Phillip A.
影响因子：
10.5
作者：
Han, Kihoon;Gennarino, Vincenzo Alessandro;Zoghbi, Huda Y.
通讯作者：
Zoghbi, Huda Y.