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

Area of Science:

• Molecular Biology
• Genomics
• Bioinformatics

Background:

• MicroRNAs (miRNAs) are key regulators of gene expression, crucial for biological processes and disease states.
• Current methods for identifying miRNA targets, like AGO-CLIP, provide indirect evidence.
• CLASH (Crosslinking, Ligation, and Sequencing of Hybrids) offers direct evidence of miRNA-target interactions within Argonaute (AGO) protein complexes.

Purpose of the Study:

• To develop CLASHub, a comprehensive online platform integrating direct miRNA-target interactions with expression data.
• To expand the available CLASH datasets across multiple species (human, mouse, Drosophila, C. elegans) and cell types.
• To provide tools for analyzing miRNA-target interactions and miRNA degradation pathways, including the role of ZSWIM8 in target-directed miRNA degradation (TDMD).

Main Methods:

• Generation of 91 new CLASH datasets from 17 cell types/tissues across four species.
• Integration of CLASH data with miRNA and messenger RNA sequencing (RNA-seq) expression data.
• Development of a user-friendly Analyzer interface for data exploration and analysis, including TDMD pathway analysis.

Main Results:

• CLASHub provides a unified resource for exploring miRNA-target interactions across diverse biological contexts.
• Analysis using CLASHub identified a TDMD trigger in the ATP6V1G1 3' UTR for miR-335-3p degradation.
• Multiple novel targets for miR-18a-5p were discovered through the CLASHub platform.

Conclusions:

• CLASHub significantly enhances the study of miRNA-target interactions by providing direct, experimentally validated data.
• The platform facilitates cell/tissue-specific exploration of miRNA regulatory networks and turnover mechanisms.
• CLASHub is a valuable resource for advancing research in miRNA biology and RNA regulation.