Article Dans Une Revue ACS Chemical Biology Année : 2025

Development of Comprehensive Screening and Assessment Assays for Small-Molecule Ligands of MALAT1 lncRNA

Résumé

RNA targeting represents an original and promising approach for the discovery of new therapeutic tools against numerous diseases. The majority of intracellular RNAs are non-coding RNAs that play key regulatory functions in many physiological processes. Among these RNAs, long non-coding RNAs (lncRNAs) constitute the largest class of non-coding transcripts and have been shown to play important functional roles in development and disease processes. In this work, we developed new biochemical assays for the discovery of efficient small molecule lncRNAs ligands selective for their target focusing on MALAT1 lncRNA. This latter bears a particular structure including a triple helical region important for its function and it has been linked to cancer cells proliferation. However, its role in cancer still needs to be completely elucidated. The application of these assays to an original library of RNA binders allowed for the discovery of unprecedented ligands of MALAT1 triple helix able to inhibit and destabilize the triple helical MALAT1 structure. The set of screening and validation assays developed could find application in the discovery of new MALAT1 binders and the new chemical scaffolds discovered in this study represent promising chemical probes for the study of the biological role of MALAT1 in disease.

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hal-05363583 , version 1 (13-11-2025)

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Mélanie Pernak, Claire Fleurisson, Cécile Delorme, Roba Moumné, Erica Benedetti, et al.. Development of Comprehensive Screening and Assessment Assays for Small-Molecule Ligands of MALAT1 lncRNA. ACS Chemical Biology, 2025, 20 (5), pp.1068-1076. ⟨10.1021/acschembio.5c00061⟩. ⟨hal-05363583⟩
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