mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability

What this study shows

Places mTOR on the RNA polymerase I branch of ribosome building. In HeLa cells, rapamycin (20 or 80 nM for 60 min) almost abolished synthesis of the 45S pre-rRNA precursor while the amounts of Pol I, UBF, TIF-IA and TIF-IB stayed the same, so mTOR acts on the activity of the transcription factor TIF-IA, not on how much machinery the cell has. Rapamycin lowered phosphorylation of TIF-IA at Ser44 and raised it at Ser199, two sites with opposite effects, weakened the TIF-IA interaction with Pol I, and after 2 h shifted TIF-IA out of the nucleus (nuclear TIF-IA roughly halved). Boundary: the authors write that mTOR activates TIF-IA either directly or indirectly, and report as data not shown that immunoprecipitated mTOR and S6K1 did NOT phosphorylate TIF-IA in vitro; Cdk2/cyclin E phosphorylates Ser44, the Ser199 kinase was not identified, and PP2A is proposed as the phosphatase that rapamycin unleashes. The nutrient link rests on a single experiment: nuclear extract from amino-acid-starved cells lost the Ser44 signal in the same way as extract from rapamycin-treated cells. Cell lines only; no animal or human data, and mTORC1 versus mTORC2 was not separated (the complexes were not yet defined in 2004).