Biology subjects

Castellanos-Rubio, A.

Publications and source records attributed to Castellanos-Rubio, A..

2 recordsLinked to original sources

bioRxiv2023

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

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.

molecular biology↗

bioRxiv2022

Nonlinear sequence similarity analysis and validation of evolutionary convergent long noncoding RNAs involved in embryonic development.

Long noncoding RNAs (lncRNAs) have been identified in almost all vertebrates, but the functional characterization of these RNA molecules is being challenging, mainly due to the lack of linear sequence homology between species. In this work, we aimed to find functional evolutionary convergent lncRNAs involved in development by screening of k-mer content (non linear similarity) and secondary structure-based approaches combined with in silico, in vitro and in vivo validation analysis. From the currently identified Madagascar gecko genes, we found a lncRNA with a similar k-mer content and structurally concordant with the human lncRNA EVX1AS. Analysis of function related characteristics together with locus-specific targeting of human and gecko EVX1AS (i.e. CRISPR Display) in human neuroepithelial cells and chicken mesencephalon confirmed that gecko Evx1as-like lncRNA mimics human EVX1AS function and induces EVX1 expression independently of the target species. Our data show functional conservation of non-homologous lncRNAs and presents a useful approach for the definition and manipulation of lncRNA function within different model organisms.

molecular biology↗