Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to metabolic stress

Chad N. Brocker; Donghwan Kim; Tisha Melia; Kritika Karri; Thomas J. Velenosi; Shogo Takahashi; Jessica A. Bonzo; David J. Waxman; Frank J. Gonzalez

LncRNAs regulate diverse cellular processes, including metabolism-related genes expressed on the opposing strand (Marin-Bejar et al., 2017; Villegas and Zaphiropoulos, 2015; Zhang et al., 2017a) . Antisense lncRNA GLS-AS is dysregulated under nutrient stress which leads to MYC elevation and stabilization (Deng et al., 2019) . The present results showed that Gm15441 negatively regulates Txnip expression during metabolic stress. LncRNA Gm15441 is antisense to Txnip, whose mRNA is decreased in liver coincident with the robust increase in Gm15441 . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/675785 doi: bioRxiv preprint expression beginning 3 hours after activation of PPARA by WY-14643. The underlying PPARA regulatory interactions controlling activation of the Gm15441 promoter region were investigated, and four of seven PPARA binding sites identified within 10 kb of the Gm15441 TSS were confirmed by ChIP assays and shown to be functional in reporter gene assays. Thus, the TXNIP anti-sense lncRNA Gm15441 is a direct target of PPARA in WY-14643-stimulated mouse liver.