Degirmenci, U., Li, J., Lim, Y.C. et al. Silencing an insulin-induced lncRNA, LncASIR, impairs the transcriptional response to insulin signalling in adipocytes. Sci Rep 9, 5608 (2019). https://doi.org/10.1038/s41598-019-42162-5
Long noncoding RNA(lncRNA)s are new regulators governing the metabolism in adipose tissue. In this study, we aimed to understand how lncRNAs respond to insulin signalling and explore whether lncRNAs have a functional role in insulin signalling pathway. We treated primary adipocyte cultures with insulin and collected RNA for RNA-sequencing to profile the non-coding transcriptome changes, through which we identified a top Adipose Specific Insulin Responsive LncRNA (LncASIR). To determine its biological function, we knocked down LncASIR using dcas9-KRAB, followed by RNA-seq to examine the effect on insulin-induced gene expression program. We identified a set of lncRNAs regulated by insulin signalling pathway. LncASIR is transcribed from a super enhancer region and responds robustly to insulin treatment. Silencing LncASIR resulted in an impaired global insulin-responsive gene program. LncASIR is a novel and integral component in the insulin signalling pathway in adipocytes.
Singapore NRF fellowship (NRF-2011NRF-NRFF 001-025), Tanoto Initiative in Diabetes Research to L.S., National Medical Research Council’s Cooperative Basic Research Grant (CBRG; NMRC/CBRG/0070/2014 and NMRC/CBRG/0101/2016), Open Fund-Individual Research (OF-IRG) Grant (NMRC/OFIRG/0062/2017), and Ministry of Education (MOE) Tier2 grant (MOE2017-T2-2-009). This work was supported by the RNA Biology Center at CSI Singapore, NUS, from funding by the Singapore Ministry of Education’s Tier 3 grants, grant number MOE2014-T3-1-006. This work was also supported by A-STAR with SINGA Ph.D. award to U.D.