Drosophila RNA polymerase III repressor Maf1 controls body size and developmental timing by modulating tRNAiMet synthesis and systemic insulin signaling.
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.
Department of Biochemistry and Molecular Biology, Clark H Smith Brain Tumour Centre, Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB, Canada T2N 4N1.
Elizabeth J
EJ
Rideout
Lynne
L
Marshall
Savraj S
SS
Grewal
D000818:Animals; D015153:Blotting, Western; D049628:Body Size / Q000502:physiology*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004330:Drosophila / Q000254:growth & development* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D019476:Insect Proteins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007814:Larva / Q000378:metabolism; D011132:Polyribosomes / Q000378:metabolism; D012320:RNA Polymerase III / Q000378:metabolism*; D012358:RNA, Transfer, Met / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology
D017931:DNA Primers; D029721:Drosophila Proteins; D019476:Insect Proteins; D007328:Insulin; C570984:Maf1 protein, Drosophila; D012358:RNA, Transfer, Met; D012097:Repressor Proteins; D012320:RNA Polymerase III; D020123:Sirolimus; D004121:Dimethyl Sulfoxide