Most mammalian mRNAs are conserved targets of microRNAs
Most mammalian mRNAs are conserved targets of microRNAs
复制标题
DOI：
10.1101/gr.082701.108
复制
发表时间：
2009-01-01
期刊：
影响因子：
7
通讯作者：
Bartel, David P.
中科院分区：
文献类型：
--
作者：
Friedman, Robin C.;Farh, Kyle Kai-How;Bartel, David P.
MicroRNA (miRNA) 是一种小的内源性 RNA，与 mRNA 中的位点配对以指导转录后抑制。许多与 miRNA 种子（核苷酸 2-7）匹配的位点，特别是 3' 非翻译区 (3'UTR) 中的位点，优先保守。在这里，我们彻底改进了用于寻找序列基序的优先保守性的工具，并将其应用于人类 3'UTR 的分析，将检测到的优先保守 miRNA 靶位点的数量增加了近三倍。新工具更有效地整合新基因组，并通过考虑突变偏差、二核苷酸保守率和单个 UTR 的保守率，更全面地控制背景保守。改进的背景模型使得能够优先检测新位点类型“偏移 6mer”的保护。总共，人类 3'UTR 内超过 45,000 个 miRNA 靶位点的保守程度高于背景水平，并且超过 60% 的人类蛋白质编码基因处于选择压力下以维持与 miRNA 的配对。哺乳动物特异性 miRNA 的保守靶点比更广泛保守的 miRNA 少得多，即使只考虑最近出现的靶点也是如此。尽管与 miRNA 3' 端配对可以补偿种子不匹配，但此类位点仅占检测到的所有优先保守位点的不到 2%。新工具能够对单个 miRNA 靶位点进行统计上强大的分析，优先保守靶向 (P-CT) 的概率与抑制的实验测量相关。我们扩展的目标预测集（包括保守的 3'-补偿位点）可在 TargetScan 网站上获取，该网站显示每个位点和每个预测目标的 P-CT。
MicroRNAs (miRNAs) are small endogenous RNAs that pair to sites in mRNAs to direct post-transcriptional repression. Many sites that match the miRNA seed (nucleotides 2-7), particularly those in 3' untranslated regions (3'UTRs), are preferentially conserved. Here, we overhauled our tool for finding preferential conservation of sequence motifs and applied it to the analysis of human 3'UTRs, increasing by nearly threefold the detected number of preferentially conserved miRNA target sites. The new tool more efficiently incorporates new genomes and more completely controls for background conservation by accounting for mutational biases, dinucleotide conservation rates, and the conservation rates of individual UTRs. The improved background model enabled preferential conservation of a new site type, the "offset 6mer," to be detected. In total, >45,000 miRNA target sites within human 3'UTRs are conserved above background levels, and >60% of human protein-coding genes have been under selective pressure to maintain pairing to miRNAs. Mammalian-specific miRNAs have far fewer conserved targets than do the more broadly conserved miRNAs, even when considering only more recently emerged targets. Although pairing to the 3' end of miRNAs can compensate for seed mismatches, this class of sites constitutes less than 2% of all preferentially conserved sites detected. The new tool enables statistically powerful analysis of individual miRNA target sites, with the probability of preferentially conserved targeting (P-CT) correlating with experimental measurements of repression. Our expanded set of target predictions (including conserved 3'-compensatory sites), are available at the TargetScan website, which displays the P-CT for each site and each predicted target.