Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction

Abstract

Through a large-scale case-control association study using 52,608 haplotype-based single nucleotide polymorphism (SNP) markers, we identified a susceptible locus for myocardial infarction (MI) on chromosome 22q12.1. Following linkage disequilibrium (LD) mapping, haplotype analyses revealed that six SNPs in this locus, all of which were in complete LD, showed markedly significant association with MI (v 2 = 25.27, P=0.0000005; comparison of allele frequency, 3,435 affected individuals versus 3,774 controls, in the case of intron 1 5,338 C>T; rs2331291). Within this locus, we isolated a complete cDNA of a novel gene, designated myocardial infarction associated transcript (MIAT). MIAT has five exons, and in vitro translation assay showed that MIAT did not encode any translational product, indicating that this is likely to be a functional RNA. In vitro functional analyses revealed that the minor variant of one SNP in exon 5 increased transcriptional level of the novel gene. Moreover, unidentified nuclear protein(s) bound more intensely to risk allele than non-risk allele. These results indicate that the altered expression of MIAT by the SNP may play some role in the pathogenesis of MI.

The interplay of LncRNA ANRIL and miR‐181b on the inflammation‐relevant coronary artery disease through mediating NF‐κB signalling pathway

“…LncRNAs, a class of non‐coding RNAs with a length greater than 200 nt, can be involved in genetic regulation transcriptionally and post‐transcriptionally, and some of them, including Bvrt, Fendrr, ANRIL, MIAT, MyHeart (Mhrt), functioned essentially in the occurrence of heart diseases, including myocardial infarction, cardiomyopathy, heart failure and atherosclerosis 23, 24, 25, 26, 27, 28. ANRIL was a 3.8‐kb‐long non‐coding RNA transcribed from chromosome 9p21, which was a crucial locus of genetic sensitivity for CAD 29, 30.…”

Long non-coding RNAs link extracellular matrix gene expression to ischemic cardiomyopathy

“…34 Another lncRNA, MIAT (myocardial infarction-associated transcript) (or Gomafu/RNCR2) was identified as a risk factor associated with patients with myocardial infarction. 35 However, how MIAT controls the status of myocardial infarction remains largely unknown. In another case, the genetic loci that encode MYH6 and MYH7, the main myosin heavy chain genes in cardiac muscle, appear to produce a non-coding antisense transcript (Myh7-as).…”

Long noncoding RNA are aberrantly expressed in vivo in the cystic fibrosis bronchial epithelium

“…They can act as decoys by binding to RNA or protein and titrating these away from other molecules; they can act as guides to direct localisation of ribonucleoprotein complexes; and they can act as scaffolds and structural platforms for nuclear processes. Aberrant expression of lncRNAs have been associated with various human conditions, including those as diverse as cancers (Yu et al, 2012), myocardial infarction (Ishii et al, 2006a) and Alzheimer"s disease (Faghihi et al, 2008). lncRNAs have been…”