Related Experiment Video
Updated: Aug 26, 2026

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability
Christine Mayer1, Jian Zhao, Xuejun Yuan
1Division of Molecular Biology of the Cell II, German Cancer Research Center, D-69120 Heidelberg, Germany.
Abstract:
In cycling cells, transcription of ribosomal RNA genes by RNA polymerase I (Pol I) is tightly coordinated with cell growth. Here, we show that the mammalian target of rapamycin (mTOR) regulates Pol I transcription by modulating the activity of TIF-IA, a regulatory factor that senses nutrient and growth-factor availability. Inhibition of mTOR signaling by rapamycin inactivates TIF-IA and impairs transcription-initiation complex formation. Moreover, rapamycin treatment leads to translocation of TIF-IA into the cytoplasm. Rapamycin-mediated inactivation of TIF-IA is caused by hypophosphorylation of Se 44 (S44) and hyperphosphorylation of Se 199 (S199). Phosphorylation at these sites affects TIF-IA activity in opposite ways, for example, phosphorylation of S44 activates and S199 inactivates TIF-IA. The results identify a new target formTOR-signaling pathways and elucidate the molecular mechanism underlying mTOR-dependent regulation of RNA synthesis.
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway
RNA Polymerase II Accessory Proteins
MAPK Signaling Cascades
General Transcription Factors

