2026-06-23T00:33:47Z https://icatplus.esrf.fr/oaipmh/request

oai:icatplus.esrf.fr:inv/2388804380 2026-05-15T23:00:11.064Z

4.2 EI 10.15151/ESRF-ES-2388804380 Stefanie JONAS Stefanie Jonas Rajiv Kumar Naresh Kumar BEDI Rajiv Kumar Naresh Kumar Bedi 0000-0002-8193-9006 Andrew MCCARTHY Andrew Mc Carthy 0000-0003-4478-0136 Stefanie JONAS Stefanie Jonas Fiona STAMM Fiona Stamm Francesco NAI Francesco Nai 0000-0002-4258-3174 Fiona STAMM Fiona Stamm Rajiv Kumar Naresh Kumar BEDI Rajiv Kumar Naresh Kumar Bedi 0000-0002-8193-9006 Amedeo CAFLISCH Amedeo Caflisch 0000-0002-2317-6792 Francesco NAI Francesco Nai 0000-0002-4258-3174 Example Institute 2029 Data from large facility measurement 2026-05-15T15:00:00Z/2026-05-15T23:00:00Z 2026-05-15T23:00:00Z I CC-BY-4.0 N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNA, regulates essential post-transcriptional processes. The reader proteins YTHDF2 and YTHDC2 specifically recognize m6A-modified RNAs, acting as central mediators of epitranscriptomic control. We employ computational modeling, structure-based drug design, and biochemical screening to identify lead compounds targeting these readers. In this proposal, we seek synchrotron beamtime to elucidate high-resolution structures of YTHDF2 and YTHDC2 in complex with our lead compounds. These structural insights will guide the optimization of potent, selective chemical probes, enabling visualization of protein–ligand interactions and mechanistic understanding of m6A-dependent regulation. Ultimately, this work will lay the groundwork for targeted therapeutic modulation of dysregulated epitranscriptomic pathways.