CLASHub: an integrated database and analytical platform for microRNA-target interactions

Abstract

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, Drosophila, and C. elegans, 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 ATP6V1G1s 3' UTR. Thus, CLASHub offers an online platform for miRNA research, enabling discovery of novel miRNA targets and triggers across diverse contexts. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=155 SRC="FIGDIR/small/668543v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@6766e4org.highwire.dtl.DTLVardef@940f40org.highwire.dtl.DTLVardef@75499dorg.highwire.dtl.DTLVardef@33f938_HPS_FORMAT_FIGEXP M_FIG C_FIG