Abstract 20439: Novel Long Intergenic Noncoding RNAs Modulate Adipose Functions in Human
Recently long intergenic noncoding RNAs (lincRNAs) have emerged as key mediators of cellular differentiation and functions in a variety of cell systems critical to cardiovascular and metabolic disorders. To identify and investigate novel functional lincRNAs in human adipose, we performed deep high-throughput RNAseq (>200 million reads/sample) in subcutaneous adiposes of 13 health volunteers. Of an integrated dataset of 54,944 human lincRNAs, 6,558 lincRNAs were detected.
Here we report 2 cytoplasmic adipose lincRNAs, linc-DMRT2 and linc-NFE2L3-1, were detected in human adipocytes but not monocytes or macrophages. Linc-DMRT2, one of the most abundant adipose lincRNAs, was markedly induced during in vitro human adipocyte differentiation. Notably, single molecule RNA FISH (fluorescence in situ hybridization) demonstrated that linc-DMRT2 were exclusively present in adipocyte cytoplasma and co-localized with processing bodies (P-bodies) marker, GW182, suggesting its potential role in modulating turnover of certain RNA species. In addition, linc-NFE2L3-1, predominantly detected in adipose and skeleton muscle, is localized near an established GWAS locus associated with waist-hip ratio adjusted BMI. We identified 4 SNPs in linc-NFE2L3-1 reaching genome wide significance for BMI (lead SNP rs10267498, P=2.73х10-8). Linkage disequilibrium analysis confirmed linc-NFE2L3-1 harbors stronger GWAS signals than protein-coding genes in the locus, suggesting lincRNA might be causal for GWAS association with BMI. Bioinformatic prediction algorithms identified potential binding sites in linc-DMRT2 and linc-NFE2L3-1 for multiple microRNAs that have been demonstrated to regulate adipogenesis (e.g. miR-15 a/b and let-7) or adipocyte functions (e.g. miR-320).
In summary, our data suggest that cytoplasmic linc-DMRT2 and linc-NFE2L3-1 may play important roles in adipocyte biology by functioning as competing endogenous RNAs and binding specific microRNAs that mediate adipocyte cellular functions. Genetic variation in such human linRNAs may contribute to cardiometabolic traits.
Author Disclosures: X. Zhang: None. R. Ballantyne: None. C. Xue: None. J.F. Ferguson: None. B. Gregory: None. M. Li: None. M.P. Reilly: None.
- © 2014 by American Heart Association, Inc.