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Isidoro-García, M (María); García-Sánchez, A. (Asunción); Sanz, C. (C.); et al. "YRNAs overexpression and potential implications in allergy". World Allergy Organization Journal. 12 (8), 2019, 100047
Small non-coding RNAs (snRNAs) develop important functions related to epigenetic regulation.
YRNAs are snRNAs involved in the initiation of DNA replication and RNA stability that regulate gene expression.
They have been related to autoimmune, cancer and inflammatory diseases but never before to allergy. In this
work we described for the first time in allergic patients the differential expression profile of YRNAs, their regulatory mechanisms and their potential as new diagnostic and therapeutic targets.
Methods: From a previous whole RNAseq study in B cells of allergic patients, differential expression profiles of
coding and non-coding transcripts were obtained. To select the most differentially expressed non coding transcripts, fold change and p-values were analyzed. A validation of the expression differences detected was developed in an independent cohort of 304 individuals, 208 allergic patients and 96 controls by using qPCR. Potential
binding and retrotransponibility capacity were characterized by in silico structural analysis. Using a novel bioinformatics approach, RNA targets identification, functional enrichment and network analyses were performed.
Results: We found that almost 70% of overexpressed non-coding transcripts in allergic patients corresponded to
YRNAs. From the three more differentially overexpressed candidates, increased expression was independently
confirmed in the peripheral blood of allergic patients. Structural analysis suggested a protein binding capacity
decrease and an increase in retrotransponibility. Studies of RNA targets allowed the identification of sequences
related to the immune mechanisms underlying allergy.
Conclusions: Overexpression of YRNAs is observed for the first time in allergic patients. Structural and functional
information points to their implication on regulatory mechanisms of the disease.