Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-018-06046-y
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Funding
- project ELIXIR-GR: The Greek Research Infrastructure for Data Management and Analysis in Life Sciences - Operational Programme Competitiveness, Entrepreneurship and Innovation (NSRF 2014-2020) [MIS 5002780]
- European Union
- General Secretariat of Research and Technology (GSRT)
- Hellenic Foundation for Research and Innovation (ELIDEK)
- IKY Foundation
- Fondation Sante
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Argonaute crosslinking and immunoprecipitation (CLIP) experiments are the most widely used high-throughput methodologies for miRNA targetome characterization. The analysis of Photoactivatable Ribonucleoside-Enhanced (PAR) CLIP methodology focuses on sequence clusters containing T-to-C conversions. Here, we demonstrate for the first time that the non-T-to-C clusters, frequently observed in PAR-CLIP experiments, exhibit functional miRNA-binding events and strong RNA accessibility. This discovery is based on the analysis of an extensive compendium of bona fide miRNA-binding events, and is further supported by numerous miRNA perturbation experiments and structural sequencing data. The incorporation of these previously neglected clusters yields an average of 14% increase in miRNA-target interactions per PAR-CLIP library. Our findings are integrated in microCLIP (www.microrna.gr/microCLIP), a cutting-edge framework that combines deep learning classifiers under a super learning scheme. The increased performance of microCLIP in CLIP-Seq-guided detection of miRNA interactions, uncovers previously elusive regulatory events and miRNA-controlled pathways.
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