Ritchie William, Legendre Matthieu, Gautheret Daniel
INSERM ERM 206, Université de la Méditerranée, 13288 Marseille, Cedex 09, France.
RNA. 2007 Apr;13(4):457-62. doi: 10.1261/rna.366507. Epub 2007 Feb 13.
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.
大多数脊椎动物基因组都转录为RNA。转录区域包含数十万种潜在的双链结构，这些结构可作为微小RNA（miRNA）成熟途径中RNA酶III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。我们在此质疑，究竟是什么特定的结构特征使得RNA茎环结构成为合适的初级或前体miRNA。我们通过使用结构比较程序RNAforester，将已知的前体miRNA与从比较基因组扫描中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，我们观察到前体miRNA与其他大小和自由能明显相似的双链结构明显聚类。与真正的miRNA前体相比，非前体双链体最显著的特征是长度增加、凸起和内部环的数量增多。由于这些特征，二级结构比较能够以惊人的准确性预测候选茎环的miRNA前体状态。此外，预测的非编码转录本比基因组DNA中随机出现的双链结构更倾向于偏离miRNA前体特征。这一结果表明，许多非编码RNA可能正在接受选择以避开RNA干扰途径。
