Li Lu, Sheng Peike, Hiers Nicholas M, Li Tianqi, Grimme Acadia L, Wang Yuzhi, Traugot Conner M, Xie Mingyi
bioRxiv. 2025 Aug 7:2025.08.05.668543. doi: 10.1101/2025.08.05.668543.
MicroRNAs (miRNAs) are ∼22-nucleotide RNAs that regulate gene expression, critical for development and disease. Residing in Argonaute (AGO) proteins, miRNAs target messenger RNAs via complementary base-pairing. Current miRNA-target databases rely on indirect data from AGO crosslinking immunoprecipitation (AGO-CLIP). In contrast, CLASH (Crosslinking, Ligation, and Sequencing of Hybrids) employs proximity ligation within AGO complexes, providing direct miRNA-target interaction evidence. Existing CLASH datasets remain limited to few human and mouse samples. CLASHub integrates CLASH-defined interactions with gene and miRNA expression data from human, mouse, , and , covering over 20 cell types and tissues. The datasets also include samples with ZSWIM8-knockout, an essential component in target RNA-directed miRNA degradation (TDMD)-a specialized mechanism for miRNA turnover triggered by basepairing with specific target RNA-thereby providing unique insights into miRNA turnover mechanisms. CLASHub also features a user-friendly Analyzer interface for CLASH, RNA-seq, miRNA-seq, and cumulative fraction curve analysis. Leveraging these tools, we uncovered a novel TDMD "trigger" for miR-335-3p degradation in 's 3' UTR. Thus, CLASHub offers an online platform for miRNA research, enabling discovery of novel miRNA targets and triggers across diverse contexts.
微小RNA(miRNA)是约22个核苷酸的RNA,可调节基因表达,这对发育和疾病至关重要。miRNA存在于AGO蛋白中,通过互补碱基配对靶向信使RNA。当前的miRNA靶标数据库依赖于AGO交联免疫沉淀(AGO-CLIP)的间接数据。相比之下,CLASH(杂交体的交联、连接和测序)在AGO复合物中采用邻近连接,提供直接的miRNA-靶标相互作用证据。现有的CLASH数据集仍然仅限于少数人类和小鼠样本。CLASHub将CLASH定义的相互作用与来自人类、小鼠、(此处原文缺失两个物种名称)的基因和miRNA表达数据整合在一起,涵盖20多种细胞类型和组织。这些数据集还包括ZSWIM8基因敲除的样本,ZSWIM8是靶RNA定向的miRNA降解(TDMD)中的一个重要组成部分,TDMD是一种由与特定靶RNA碱基配对触发的miRNA周转的特殊机制,从而为miRNA周转机制提供了独特的见解。CLASHub还具有一个用户友好的分析器界面,用于CLASH、RNA测序、miRNA测序和累积分数曲线分析。利用这些工具,我们在(此处原文缺失物种名称)的3'UTR中发现了一种新的miR-335-3p降解的TDMD“触发因素”。因此,CLASHub为miRNA研究提供了一个在线平台,能够在不同背景下发现新的miRNA靶标和触发因素。