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m6A Methylated Long Noncoding RNA LOC339803 Regulates Intestinal Inflammatory Response
Ane Olazagoitia-Garmendia1,2,3, Henar Rojas-Márquez2,3, Maialen Sebastian-delaCruz2,3
1Department of Biochemistry and Molecular Biology, University of the Basque Country UPV/EHU, Leioa, 48940, Spain.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|January 26, 2024
Summary
Methylated long noncoding RNA LOC339803 drives intestinal inflammation by regulating cytokine production. Targeting LOC339803 offers a potential therapeutic strategy for inflammatory bowel diseases.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- Chronic inflammation underlies complex diseases, with mechanisms often unclear.
- Long noncoding RNAs (lncRNAs) are implicated in inflammatory disorders.
- RNA modifications like m6A impact lncRNA function and disease predisposition.
Purpose of the Study:
- To investigate the role of the intestinal inflammation-associated lncRNA LOC339803 in cytokine production.
- To elucidate the molecular mechanisms linking LOC339803, RNA methylation, and intestinal inflammation.
Main Methods:
- Analysis of allele-specific m6A methylation and its effect on protein binding.
- Investigation of the LOC339803-YTHDC1 interaction and chromatin localization.
- Validation in human intestinal biopsy samples and in vitro/ex vivo models.
Main Results:
- Allele-specific m6A methylation of LOC339803 influences YTHDC1 binding.
- LOC339803 interaction with YTHDC1 affects chromatin localization and NFκB-mediated cytokine expression.
- LOC339803 targeting demonstrated therapeutic potential in preclinical models.
Conclusions:
- Methylated LOC339803 is a key mediator of intestinal inflammation.
- This lncRNA explains genetic susceptibility to inflammatory bowel diseases.
- LOC339803 represents a promising therapeutic target for inflammatory intestinal disorders.
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