RNA stem-loops: To be or not to be cleaved by RNAse III

RNA stem-loops: To be or not to be cleaved by RNAse III
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DOI:
10.1261/rna.366507
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发表时间:
2007-04-01
期刊:
RNA
影响因子:
4.5
通讯作者:
Gautheret, Daniel
Gautheret, Daniel
中科院分区:
生物学3区
文献类型:
--
作者:
Ritchie, William;Legendre, Matthieu;Gautheret, Daniel

文献摘要

被引文献

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大多数脊椎动物基因组被转录成RNA。转录区域包含数十万个潜在的双链体结构,可以作为 microRNA (miRNA) 成熟途径的 RNAse III 酶的底物。然而,这些潜在前体中只有少数能够进入细胞质形成成熟的 miRNA。我们在这里质疑什么特定的结构特征使 RNA 茎环结构成为足够的初级或前体 miRNA。我们通过使用结构比较程序 RNAforester 将已知的 pre-miRNA 与从比较基因组扫描获得的其他预测非编码转录本进行比较来解决这个问题。通过分析 1200 个此类 RNA 结构的分类树,我们观察到 pre-miRNA 的簇与大小和自由能明显相似的其他双链体结构明显不同。与真正的 miRNA 前体相比,非前体双链体最显着的特征是长度以及凸起和内部环的数量增加。由于这些特征,二级结构比较可以以惊人的准确性预测候选茎环的 miRNA 前体状态。此外,与基因组 DNA 中随机出现的双链结构相比,预测的非编码转录本更倾向于偏离 miRNA 前体特征。这一结果表明,许多非编码 RNA 可能会被选择来躲避 RNAi 途径。
Most of the vertebrate genome is transcribed into RNA. Transcribed regions contain hundreds of thousands of potential duplex structures that could serve as substrates for RNAse III enzymes of microRNA (miRNA) maturation pathways. Yet, only a minority of these potential precursors make their way to the cytoplasm to form mature miRNAs. We question here what specific structural features make an RNA stem-loop structure an adequate primary or precursor miRNA. We address this question by comparing known pre-miRNAs to other predicted noncoding transcripts obtained from comparative genomics scans, using the structure comparison program RNAforester. By analyzing a classification tree of 1200 such RNA structures, we observe that pre-miRNAs cluster distinctly from other duplex structures of apparently similar size and free energy. The most distinctive features of nonprecursor duplexes are increased lengths and numbers of bulges and internal loops when compared to real miRNA precursors. Thanks to these characteristics, secondary structure comparison can predict the miRNA precursor status of a candidate stem-loop with a surprising accuracy. Furthermore, predicted noncoding transcripts tend to depart from miRNA precursor characteristics more strongly than randomly occurring duplex structures in genomic DNA. This result suggests that many noncoding RNAs may be under selection to dodge the RNAi pathway.