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RRN3  -  RRN3 RNA polymerase I transcription factor...

Homo sapiens

Synonyms: A-270G1.2, DKFZp566E104, RNA polymerase I-specific transcription initiation factor RRN3, TIF-IA, TIFIA, ...
 
 
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Disease relevance of RRN3

  • We have partially purified these proteins from cultured Ehrlich ascites cells and show that in the presence of TIF-IA and TIF-IB, pol I directs very low amounts of specific transcripts [1].
 

High impact information on RRN3

  • Phosphorylation at these sites affects TIF-IA activity in opposite ways, for example, phosphorylation of S44 activates and S199 inactivates TIF-IA [2].
  • Rapamycin-mediated inactivation of TIF-IA is caused by hypophosphorylation of Se 44 (S44) and hyperphosphorylation of Se 199 (S199) [2].
  • These include a range of nuclear substrates, including transcription factors and nuclear hormone receptors, heterogeneous nuclear ribonucleoprotein K, and the Pol I-specific transcription factor TIF-IA, which regulates ribosome synthesis [3].
  • Here we show that growth factors induce rRNA synthesis by activating MAPK-dependent signaling cascades that target the RNA polymerase I-specific transcription initiation factor TIF-IA [4].
  • Replacement of S649 by alanine inactivates TIF-IA, inhibits pre-rRNA synthesis, and retards cell growth [4].
 

Biological context of RRN3

  • The association with Pol I requires phosphorylation of TIF-IA at Ser 649 by RSK kinase, indicating a role for NMI in the growth-dependent regulation of rRNA synthesis [5].
  • We conclude that hRRN3 functions to recruit initiation-competent Pol I to rRNA gene promoters [6].
  • The nucleolar target for down-regulation of rDNA transcription is TIF-IA, an essential transcription factor that modulates the activity of RNA polymerase I (Pol I) [7].
 

Associations of RRN3 with chemical compounds

  • In mammals, growth-dependent regulation of RNA polymerase I (Pol I) transcription is mediated by TIF-IA, an essential initiation factor that is active in extracts from growing but not starved or cycloheximide-treated mammalian cells [8].
 

Physical interactions of RRN3

  • Whereas actin associated with Pol I, NMI bound to Pol I through the transcription-initiation factor TIF-IA [5].
  • Using a reconstituted transcription system consisting of purified transcription factors, we demonstrate that TIF-IA is a bona fide transcription initiation factor which interacts with RNA polymerase I. Preinitiation complexes can be assembled in the absence of TIF-IA, but formation of the first phosphodiester bonds of nascent rRNA is precluded [9].
 

Enzymatic interactions of RRN3

 

Other interactions of RRN3

 

Analytical, diagnostic and therapeutic context of RRN3

  • Here we report the molecular cloning and functional characterization of recombinant TIF-IA, which turns out to be the mammalian homolog of the yeast factor Rrn3p [8].

References

  1. Trans-acting factors involved in species-specificity and control of mouse ribosomal gene transcription. Schnapp, A., Rosenbauer, H., Grummt, I. Mol. Cell. Biochem. (1991) [Pubmed]
  2. mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability. Mayer, C., Zhao, J., Yuan, X., Grummt, I. Genes Dev. (2004) [Pubmed]
  3. Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases. Bogoyevitch, M.A., Kobe, B. Microbiol. Mol. Biol. Rev. (2006) [Pubmed]
  4. ERK-dependent phosphorylation of the transcription initiation factor TIF-IA is required for RNA polymerase I transcription and cell growth. Zhao, J., Yuan, X., Frödin, M., Grummt, I. Mol. Cell (2003) [Pubmed]
  5. Nuclear actin and myosin I are required for RNA polymerase I transcription. Philimonenko, V.V., Zhao, J., Iben, S., Dingová, H., Kyselá, K., Kahle, M., Zentgraf, H., Hofmann, W.A., de Lanerolle, P., Hozák, P., Grummt, I. Nat. Cell Biol. (2004) [Pubmed]
  6. hRRN3 is essential in the SL1-mediated recruitment of RNA Polymerase I to rRNA gene promoters. Miller, G., Panov, K.I., Friedrich, J.K., Trinkle-Mulcahy, L., Lamond, A.I., Zomerdijk, J.C. EMBO J. (2001) [Pubmed]
  7. Cellular stress and nucleolar function. Mayer, C., Grummt, I. Cell Cycle (2005) [Pubmed]
  8. TIF-IA, the factor mediating growth-dependent control of ribosomal RNA synthesis, is the mammalian homolog of yeast Rrn3p. Bodem, J., Dobreva, G., Hoffmann-Rohrer, U., Iben, S., Zentgraf, H., Delius, H., Vingron, M., Grummt, I. EMBO Rep. (2000) [Pubmed]
  9. Function of the growth-regulated transcription initiation factor TIF-IA in initiation complex formation at the murine ribosomal gene promoter. Schnapp, A., Schnapp, G., Erny, B., Grummt, I. Mol. Cell. Biol. (1993) [Pubmed]
 
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