Work

Metabolic programming a lean phenotype by deregulation of RNA polymerase III

Year: 2018

Type: article

Abstract: Significance As a repressor of transcription by RNA polymerase (Pol) III, Maf1 is thought to play an important role in the energetic economy of cells by controlling the synthesis of highly abundant tRNAs and 5S rRNA. Accordingly, Maf1 knockout mice are lean, resist weight gain on normal and high fat diets, and up-regulate catabolic processes to meet their increased demand for cellular energy. The origin of this energy demand is proposed to reside in a futile cycle of RNA synthesis and turnover that is enhanced by constitutive Pol III transcription. We present metabolomic evidence supporting this mechanism. We find that central metabolic pathways are reprogrammed in the liver of Maf1 knockout mice to direct substrates toward energy generation and nucleotide synthesis.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1815590115

Authors: Ian M. Willis, Robyn D. Moir, Nouria Hernandez

Institutions: Albert Einstein College of Medicine, University of Lausanne

Language: English

Topic: RNA and protein synthesis mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases

Awards: MAF1 Function and Metabolic Inefficiency, Mechanisms of basal and regulated mammalian RNA polymerase III transcription, New York Obesity Research Center, Cancer Center Support Grant, NYR-Diabetes Research Center (NYR-DRC)