TY - JOUR T1 - AUF-1 knock down in mice overarches butyrate driven hypo-cholesteraemia by conjuring AUF-1-Dicer-1-miR122 hierarchy JF - bioRxiv DO - 10.1101/2022.06.13.496022 SP - 2022.06.13.496022 AU - Oishika Das AU - Jayanta Kundu AU - Atanu Ghosh AU - Anupam Gautam AU - Souradeepa Ghosh AU - Mainak Chakraborty AU - Aaheli Masid AU - Samiran Sona Gauri AU - Debmalya Mitra AU - Moumita Dutta AU - Budhaditya Mukherjee AU - Surajit Sinha AU - Moumita Bhaumik Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/06/16/2022.06.13.496022.abstract N2 - This discourse probes the mechanistic molecular details of butyrate action in maintaining host-cholesterol balance. Hepatic miR122 being the most indispensable regulator of cholesterol metabolic enzymes, we studied upstream players of miR122 biogenesis in the presence and absence of butyrate in Huh7 cells and mice model. We showed that butyrate treatment caused upregulation of RNA-binding protein, AUF-1 resulting in RNase-III nuclease, Dicer-1 instability, and significant diminution of miR122. We proved its importance of AUF-1 and sequential downstream players in AUF-1-knock-down mice. We synthesized unique self-transfecting GMO (guanidinium-morpholino-oligonucleotides) linked PMO (Phosphorodiamidate-Morpholino Oligonucleotides)-based antisense reagent and injection of which in mouse caused near absence of AUF-1 coupled with increased Dicer-1 and miR122, and reduced serum cholesterol regardless of butyrate treatment indicating that butyrate acts though AUF-1. The roster of intracellular players was as follows: AUF-1-Dicer-1-miR122 for triggering butyrate driven hypocholesterlaemia. To our knowledge this is the first report linking AUF-1 with cholesterol biogenesis.Competing Interest StatementThe authors have declared no competing interest. ER -