RRC ID |
50063
|
著者 |
Sriskanthadevan-Pirahas S, Deshpande R, Lee B, Grewal SS.
|
タイトル |
Ras/ERK-signalling promotes tRNA synthesis and growth via the RNA polymerase III repressor Maf1 in Drosophila.
|
ジャーナル |
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.
|
巻・号 |
14(2)
|
ページ |
e1007202
|
公開日 |
2018-2-1
|
DOI |
10.1371/journal.pgen.1007202
|
PII |
PGENETICS-D-17-00811
|
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 |
5.175
|
引用数 |
9
|
リソース情報 |
ショウジョウバエ |
4155R-1
4155R-2 |