Composition of seed sequence is a major determinant of microRNA targeting patterns
Composition of seed sequence is a major determinant of microRNA targeting patterns
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DOI：
10.1093/bioinformatics/btu045
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发表时间：
2014-05-15
期刊：
影响因子：
5.8
通讯作者：
Wang, Xiaowei
中科院分区：
文献类型：
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作者：
Wang, Xiaowei
MicroRNAs（miRNAs）是一类广泛参与基因表达调控的小分子非编码RNA。功能性miRNA研究中的一个主要障碍是miRNA靶向基因的可靠预测，因为定义miRNA靶向识别的规则迄今为止还没有很好地建立。从最近的CLASH（交联，连接和测序的杂交）研究的高通量实验数据的可用性提出了一个前所未有的机会，以表征miRNA的目标识别模式，这可能会提供指导，提高miRNA的目标prediction.Results：的CLASH数据进行了分析，以确定独特的序列特征，典型和非典型的miRNA目标类型。大多数miRNA靶是非典型类型的，即不涉及与典型miRNA种子区的完美配对。不同的miRNA具有不同的靶向模式，并且这种miRNA到miRNA的变异性与种子序列组成相关。具体而言，基于种子的典型靶标识别依赖于miRNA种子的GC含量。对于种子区GC含量低的miRNAs，非经典靶向是靶标识别的主要机制。与经典靶向相反，非经典靶向在RNA或蛋白质水平上均不导致显著的靶向下调。
Motivation: 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.Results: 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.