Biology subjects

Olazagoitia-Garmendia, A.

Publications and source records attributed to Olazagoitia-Garmendia, A..

3 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

The type 1 diabetes-associated lncRNA ARGI participates in virus-induced pancreatic beta cell inflammation.

Type 1 diabetes-associated single nucleotide polymorphisms are mainly located in non-coding regions of the human genome. Single nucleotide polymorphisms located in long non-coding RNAs may result in the disruption of their secondary structure, affecting their function. Here, we functionally characterized the virus-induced type 1 diabetes-associated lncRNA ARGI (Antiviral Response Gene Inducer). ARGI upregulation in pancreatic {beta} cells leads to the transcriptional activation of antiviral and pro-inflammatory genes. Upon a viral insult, ARGI is upregulated in the nuclei of pancreatic {beta} cells and binds to CTCF to interact with the regulatory regions of IFN{beta} and interferon-stimulated genes, promoting their transcriptional activation in an allele-specific manner. The presence of the risk allele for type 1 diabetes in ARGI induces an hyperactivation of type I IFN response in {beta} cells, an expression signature that is present in the pancreas of diabetic patients. These data shed light on the molecular mechanisms by which type 1 diabetes-related single nucleotide polymorphisms in long non-coding RNAs influence pathogenesis at the pancreatic {beta} cell level.

genetics↗

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↗