AMP-activated protein kinase adapts rRNA synthesis to cellular energy supply.
AMP-activated protein kinase (AMPK) senses changes in the intracellular AMP/ATP ratio, switching off energy-consuming processes and switching on catabolic pathways in response to energy depletion. Here, we show that AMPK down-regulates rRNA synthesis under glucose restriction by phosphorylating the RNA polymerase I (Pol I)-associated transcription factor TIF-IA at a single serine residue (Ser-635). Phosphorylation by AMPK impairs the interaction of TIF-IA with the TBP-containing promoter selectivity factor SL1, thereby precluding the assembly of functional transcription initiation complexes. Mutation of Ser-635 compromises down-regulation of Pol I transcription in response to low energy supply, supporting that activation of AMPK adapts rRNA synthesis to nutrient availability and the cellular energy status.
Hoppe
Sven
S
Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, INF 581, D-69120 Heidelberg, Germany.
Bierhoff
Holger
H
Cado
Ivana
I
Weber
Andrea
A
Tiebe
Marcel
M
Grummt
Ingrid
I
Voit
Renate
R
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D035463:Pol1 Transcription Initiation Complex Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012318:RNA Polymerase I / Q000378:metabolism; D012335:RNA, Ribosomal / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D014158:Transcription, Genetic
D035463:Pol1 Transcription Initiation Complex Proteins; D012335:RNA, Ribosomal; C428423:RRN3 protein, human; D011994:Recombinant Proteins; C091129:TAF1B protein, human; D012694:Serine; D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases; D012318:RNA Polymerase I; D005947:Glucose