Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases / metabolism*
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Adenosine Triphosphate / metabolism
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Animals
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Cell Line
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Energy Metabolism
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Glucose / metabolism
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Humans
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Mice
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Models, Biological
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NIH 3T3 Cells
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Phosphorylation
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Pol1 Transcription Initiation Complex Proteins / antagonists & inhibitors
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Pol1 Transcription Initiation Complex Proteins / chemistry
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Pol1 Transcription Initiation Complex Proteins / genetics
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Pol1 Transcription Initiation Complex Proteins / metabolism
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RNA Polymerase I / metabolism
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RNA, Ribosomal / biosynthesis*
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Serine / chemistry
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Transcription, Genetic
Substances
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Pol1 Transcription Initiation Complex Proteins
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RNA, Ribosomal
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RRN3 protein, human
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Recombinant Proteins
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TAF1B protein, human
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Serine
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Adenosine Triphosphate
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AMP-Activated Protein Kinases
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RNA Polymerase I
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Glucose