A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence
A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence
复制标题
DOI：
10.1073/pnas.0803230105
复制
发表时间：
2008-09-30
影响因子：
11.1
通讯作者：
Coller, Hilary A.
中科院分区：
文献类型：
--
作者：
Forman, Joshua J.;Legesse-Miller, Aster;Coller, Hilary A.
据报道，microRNA（miRNAs）的识别位点位于转录物的3'非翻译区。在对编码区内高度保守的基序的计算筛选中，我们发现人类基因组中编码区内在核苷酸水平上保守的序列过多，其中得分最高的是富含miRNA靶序列。为了验证我们的结果，我们通过实验证明let-7 miRNA直接靶向其编码序列内的miRNA加工酶Dicer，从而建立了miRNA/Dicer自动调节负反馈环的机制。我们还发现计算证据表明，编码区和3'UTR中的miRNA靶位点可能在机制上不同。这项工作表明，在动物中，miRNAs可以直接靶向其编码区内的转录本，这表明，对miRNAs调控靶点的完整搜索应该扩展到包括其编码区内具有识别位点的基因。随着越来越多的基因组被测序，我们用于识别具有高序列保守性的基序的方法学方法对于检测编码区内的功能序列基序将越来越有价值。
Recognition sites for microRNAs (miRNAs) have been reported to be located in the 3' untranslated regions of transcripts. In a computational screen for highly conserved motifs within coding regions, we found an excess of sequences conserved at the nucleotide level within coding regions in the human genome, the highest scoring of which are enriched for miRNA target sequences. To validate our results, we experimentally demonstrated that the let-7 miRNA directly targets the miRNA-processing enzyme Dicer within its coding sequence, thus establishing a mechanism for a miRNA/Dicer autoregulatory negative feedback loop. We also found computational evidence to suggest that miRNA target sites in coding regions and 3' UTRs may differ in mechanism. This work demonstrates that miRNAs can directly target transcripts within their coding region in animals, and it suggests that a complete search for the regulatory targets of miRNAs should be expanded to include genes with recognition sites within their coding regions. As more genomes are sequenced, the methodological approach that we used for identifying motifs with high sequence conservation will be increasingly valuable for detecting functional sequence motifs within coding regions.