Thomas Laurent F, Sætrom Pål
Department of Cancer Research and Molecular Medicine and Department of Computer and Information Science, Norwegian University of Science and Technology, N-7489 Trondheim, Norway.
Department of Cancer Research and Molecular Medicine and Department of Computer and Information Science, Norwegian University of Science and Technology, N-7489 Trondheim, NorwayDepartment of Cancer Research and Molecular Medicine and Department of Computer and Information Science, Norwegian University of Science and Technology, N-7489 Trondheim, Norway.
Bioinformatics. 2014 Aug 15;30(16):2243-6. doi: 10.1093/bioinformatics/btu257. Epub 2014 Apr 24.
Circular RNAs (circRNAs) are an abundant class of highly stable RNAs that can affect gene regulation by binding and preventing microRNAs (miRNAs) from regulating their messenger RNA (mRNA) targets. Mammals have thousands of circRNAs with predicted miRNA binding sites, but only two circRNAs have been verified as being actual miRNA sponges. As it is unclear whether these thousands of predicted miRNA binding sites are functional, we investigated whether miRNA seed sites within human circRNAs are under selective pressure.
Using SNP data from the 1000 Genomes Project, we found a significant decrease in SNP density at miRNA seed sites compared with flanking sequences and random sites. This decrease was similar to that of miRNA seed sites in 3' untranslated regions, suggesting that many of the predicted miRNA binding sites in circRNAs are functional and under similar selective pressure as miRNA binding sites in mRNAs.
环状RNA（circRNA）是一类丰富的高度稳定的RNA，其可通过结合并阻止微小RNA（miRNA）调控其信使RNA（mRNA）靶标来影响基因调控。哺乳动物拥有数千个具有预测miRNA结合位点的circRNA，但仅有两个circRNA已被证实为实际的miRNA海绵。由于尚不清楚这数千个预测的miRNA结合位点是否具有功能，我们研究了人类circRNA中的miRNA种子位点是否受到选择压力。
利用千人基因组计划的SNP数据，我们发现与侧翼序列和随机位点相比，miRNA种子位点的SNP密度显著降低。这种降低与3'非翻译区中miRNA种子位点的降低相似，表明circRNA中许多预测的miRNA结合位点具有功能，并且受到与mRNA中miRNA结合位点相似的选择压力。
