mTORC1 directly phosphorylates and regulates human MAF1.
mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the phosphorylations nor the kinase involved is known. We find that human MAF1 is absolutely required for pol III repression in response to serum starvation or TORC1 inhibition by rapamycin or Torin1. The protein is phosphorylated mainly on residues S60, S68, and S75, and this inhibits its pol III repression function. The responsible kinase is mTORC1, which phosphorylates MAF1 directly. Our results describe molecular mechanisms by which mTORC1 controls human MAF1, a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1.
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Annemieke A
AA
Michels
Aaron M
AM
Robitaille
Diane
D
Buczynski-Ruchonnet
Wassim
W
Hodroj
Jaime H
JH
Reina
Michael N
MN
Hall
Nouria
N
Hernandez
D006801:Humans; D010766:Phosphorylation; D012320:RNA Polymerase III / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D020123:Sirolimus / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
D012320:RNA Polymerase III; D020123:Sirolimus