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bioRxiv · 10.1101/2023.01.17.524371

m6A methylated long noncoding RNA regulates proinflammatory response emerging as novel target for IBD

Olazagoitia-Garmendia, A.·Rojas-Marquz, H.·Sebastian-delaCruz, M.·Ochoa, A.·Mendoza-Gomez, L. M.·Huerta, A.·Santin, I.·Castellanos-Rubio, A.
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Abstract

Cytokine mediated sustained inflammation increases the risk to develop different complex chronic inflammatory diseases, such as inflammatory bowel disease (IBD). Recent studies highlighted the involvement of inflammation associated gene variants in m6A methylation. Moreover, long noncoding RNAs (lncRNAs) participate in the pathogenesis of inflammatory disorders and their function can be influenced by differential methylation. Here we describe the functional implication of LOC339803 lncRNA in the development of IBD. We found that allele-specific m6A methylation affects YTHDC1 mediated protein binding affinity. LOC339803-YTHDC1 interaction dictates chromatin localization of LOC339803 ultimately inducing IL1B and contributing to the development of intestinal inflammation. Our findings were confirmed using human intestinal biopsy samples from IBD and controls. Overall, our results support LOC339803 lncRNA as an important mediator of intestinal inflammation, presenting this lncRNA as a potential novel therapeutic target for the treatment of IBD.

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Olazagoitia-Garmendia, A., Rojas-Marquz, H., Sebastian-delaCruz, M., Ochoa, A., Mendoza-Gomez, L. M., Huerta, A., Santin, I., Castellanos-Rubio, A.. 2023-01-17. m6A methylated long noncoding RNA regulates proinflammatory response emerging as novel target for IBD. https://doi.org/10.1101/2023.01.17.524371

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