MiRNAs mediate mTORC1 effects

Abstract

Signal Transduction Too much signaling by the mammalian target of rapamycin complex 1 (mTORC1) protein kinase complex is a bad thing in part because it enhances production of particular microRNAs (miRNAs). Mouse cells engineered to lack the mTORC1 inhibitor component Tsc1 and thus exhibit excessive mTORC1 signaling also showed altered glucose metabolism. Liko et al. traced this effect to enhanced production of miRNAs from an imprinted locus (that is, expressed from the alleles from one parent of origin only) on chromosome 12. Expression of these miRNAs increased production of enzymes that catalyze gluconeogenesis and resulted in glucose intolerance. Precisely how the miRNAs work is unclear, but they may provide a previously unrecognized target for managing metabolic diseases. Proc. Natl. Acad. Sci. U.S.A. 117 , 1524 (2020).