Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 4, Pages 1139-1144Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1113311109
Keywords
metabolism; physiology; endocrinology; amino acids; adipose tissue
Categories
Funding
- Canadian Institutes of Health Research [MOP-86622]
- Alberta Cancer Foundation
- Natural Sciences and Engineering Council of Canada
- Alberta Innovates-Health Solutions
- Canadian Institutes of Health Research (Alberta Children's Hospital Research Institute for Child and Maternal Health)
- Alberta Health Services (Alberta Cancer Foundation/Alberta Cancer Board)
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The target-of-rapamycin pathway couples nutrient availability with tissue and organismal growth in metazoans. The key effectors underlying this growth are, however, unclear. Here we show that Maf1, a repressor of RNA polymerase III-dependent tRNA transcription, is an important mediator of nutrient-dependent growth in Drosophila. We find nutrients promote tRNA synthesis during larval development by inhibiting Maf1. Genetic inhibition of Maf1 accelerates development and increases body size. These phenotypes are due to a non-cell-autonomous effect of Maf1 inhibition in the fat body, the main larval endocrine organ. Inhibiting Maf1 in the fat body increases growth by promoting the expression of brain-derived insulin-like peptides and consequently enhanced systemic insulin signaling. Remarkably, the effects of Maf1 inhibition are reproduced in flies carrying one extra copy of the initiator methionine tRNA, tRNA(i)(Met). These findings suggest the stimulation of tRNA(i)(Met) synthesis via inhibition of dMaf1 is limiting for nutrition-dependent growth during development.
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