Assessment of microRNA-related SNP effects in the 3′ untranslated region of the IL22RA2 risk locus in multiple sclerosis

Abstract

Recent large-scale association studies have identified over 100 MS risk loci. One of these MS risk variants is single-nucleotide polymorphism (SNP) rs17066096, located 14 kb downstream of IL22RA2. IL22RA2 represents a compelling MS candidate gene due to the role of IL-22 in autoimmunity; however, rs17066096 does not map into any known functional element. We assessed whether rs17066096 or a nearby proxy SNP may exert pathogenic effects by affecting microRNA-to-mRNA binding and thus IL22RA2 expression using comprehensive in silico predictions, in vitro reporter assays, and genotyping experiments in 6,722 individuals. In silico screening identified two predicted microRNA binding sites in the 3′UTR of IL22RA2 (for hsa-miR-2278 and hsamiR-411-5p) encompassing a SNP (rs28366) in moderate linkage disequilibrium with rs17066096 (r 2 =0.4). The binding of both microRNAs to the IL22RA2 3′UTR was confirmed in vitro, but their binding affinities were not significantly affected by rs28366. Association analyses revealed significant Electronic supplementary material The online version of this article

MicroRNA-138 is a potential regulator of memory performance in humans

“…Experiments were performed as previously described (Lill et al, 2014). Custom made reporter plasmids (pLightSwitch_3UTR) containing the appropriate 3′UTR sequence and the miRNA mimics were purchased from SwitchGear Genomics (Menlo Park, CA, USA).…”

“…In this study, we specifically searched for memory-associated DNA sequence variants predicted to affect miRNA-to-mRNA binding using a similar strategy as described previously by our group (Lill et al, 2014). Genetic associations, with measures of both working and episodic memory functions were assessed via genome-wide screening as part of an ongoing GWAS in participants of the Berlin Aging Study II (BASE-II).…”

Genome-wide significant association with seven novel multiple sclerosis risk loci

“…However, the Dutch effect size estimates were similar to the remaining western European data sets suggesting that undetected population stratification may not have substantially biased the results. In addition, the western European data sets have been used previously in multiple similar studies nearly always resulting in association findings in line with those from independent GWAS (eg, refs 3 20 21). Furthermore, none of the meta-analysis results was driven by a single outlying study effect estimate.…”

Revealing genome-wide mRNA and microRNA expression patterns in leukemic cells highlighted “hsa-miR-2278” as a tumor suppressor for regain of chemotherapeutic imatinib response due to targeting STAT5A

“…b While hsa-miR-1245b-3p expression was 2.92-fold upregulated (p<0.0 001), it was decreased by 2.75-fold (p= 0.0001) following transfection either with mimic or inhibitor, respectively stands for the maximally expressed miRNA in our imatinib resistant cells. Whereas only one paper for hsa-miR-2278 could be found, which was in a totally different topic as a SNP analyses (rs28366) for IL22RA2 and to define whether hsa-miR-2278 binding affinity was significantly affected by this SNP [15].…”