Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63108, USA.
Bioinformatics. 2014 May 15;30(10):1377-83. doi: 10.1093/bioinformatics/btu045. Epub 2014 Jan 26.
MicroRNAs (miRNAs) are small non-coding RNAs that are extensively involved in gene expression regulation. One major roadblock in functional miRNA studies is the reliable prediction of genes targeted by miRNAs, as rules defining miRNA target recognition have not been well-established to date. Availability of high-throughput experimental data from a recent CLASH (cross linking, ligation and sequencing of hybrids) study has presented an unprecedented opportunity to characterize miRNA target recognition patterns, which may provide guidance for improved miRNA target prediction.
The CLASH data were analysed to identify distinctive sequence features that characterize canonical and non-canonical miRNA target types. Most miRNA targets were of non-canonical type, i.e. without involving perfect pairing to canonical miRNA seed region. Different miRNAs have distinct targeting patterns, and this miRNA-to-miRNA variability was associated with seed sequence composition. Specifically, seed-based canonical target recognition was dependent on the GC content of the miRNA seed. For miRNAs with low GC content of the seed region, non-canonical targeting was the dominant mechanism for target recognition. In contrast to canonical targeting, non-canonical targeting did not lead to significant target downregulation at either the RNA or protein level.
微小 RNA（miRNA）是广泛参与基因表达调控的小非编码 RNA。功能 miRNA 研究的一个主要障碍是可靠地预测 miRNA 靶向的基因，因为迄今为止尚未建立定义 miRNA 靶识别规则。最近 CLASH（杂交体的交联、连接和测序）研究中的高通量实验数据的可用性提供了一个前所未有的机会来描述 miRNA 靶识别模式，这可能为改进 miRNA 靶预测提供指导。
对 CLASH 数据进行了分析，以确定可区分特征，这些特征可表征规范和非规范 miRNA 靶类型。大多数 miRNA 靶标是非规范类型，即不涉及与规范 miRNA 种子区的完全配对。不同的 miRNA 具有不同的靶向模式，这种 miRNA 到 miRNA 的可变性与种子序列组成有关。具体而言，基于种子的规范靶标识别取决于 miRNA 种子的 GC 含量。对于种子区域 GC 含量低的 miRNA，非规范靶向是靶标识别的主要机制。与规范靶向不同，非规范靶向不会导致 RNA 或蛋白质水平的显著靶向下调。
