RRC ID 50063
Author Sriskanthadevan-Pirahas S, Deshpande R, Lee B, Grewal SS.
Title Ras/ERK-signalling promotes tRNA synthesis and growth via the RNA polymerase III repressor Maf1 in Drosophila.
Journal PLoS Genet.
Abstract The small G-protein Ras is a conserved regulator of cell and tissue growth. These effects of Ras are mediated largely through activation of a canonical RAF-MEK-ERK kinase cascade. An important challenge is to identify how this Ras/ERK pathway alters cellular metabolism to drive growth. Here we report on stimulation of RNA polymerase III (Pol III)-mediated tRNA synthesis as a growth effector of Ras/ERK signalling in Drosophila. We find that activation of Ras/ERK signalling promotes tRNA synthesis both in vivo and in cultured Drosophila S2 cells. We also show that Pol III function is required for Ras/ERK signalling to drive proliferation in both epithelial and stem cells in Drosophila tissues. We find that the transcription factor Myc is required but not sufficient for Ras-mediated stimulation of tRNA synthesis. Instead we show that Ras signalling promotes Pol III function and tRNA synthesis by phosphorylating, and inhibiting the nuclear localization and function of the Pol III repressor Maf1. We propose that inhibition of Maf1 and stimulation of tRNA synthesis is one way by which Ras signalling enhances protein synthesis to promote cell and tissue growth.
Volume 14(2)
Pages e1007202
Published 2018-2
DOI 10.1371/journal.pgen.1007202
PMID 29401457
PMC PMC5814106
MeSH Animals Animals, Genetically Modified Cell Proliferation / genetics Cells, Cultured Drosophila Proteins / genetics Drosophila Proteins / physiology* Drosophila melanogaster / embryology Drosophila melanogaster / genetics* Embryo, Nonmammalian MAP Kinase Signaling System / physiology* Protein Biosynthesis / genetics RNA Polymerase III / antagonists & inhibitors RNA, Transfer / biosynthesis* RNA, Transfer / genetics Repressor Proteins / genetics Repressor Proteins / physiology* Signal Transduction / physiology Transcription Elongation, Genetic* Transcription Factor TFIIIB / genetics Transcription Factor TFIIIB / physiology Wings, Animal / embryology Wings, Animal / metabolism ras Proteins / physiology*
IF 5.224
Drosophila 4155R-1 4155R-2