UBF activates RNA polymerase I transcription by stimulating promoter escape.
Ribosomal RNA gene transcription by RNA polymerase I (Pol I) is the driving force behind ribosome biogenesis, vital to cell growth and proliferation. The key activator of Pol I transcription, UBF, has been proposed to act by facilitating recruitment of Pol I and essential basal factor SL1 to rDNA promoters. However, we found no evidence that UBF could stimulate recruitment or stabilization of the pre-initiation complex (PIC) in reconstituted transcription assays. In this, UBF is fundamentally different from archetypal activators of transcription. Our data imply that UBF exerts its stimulatory effect on RNA synthesis, after PIC formation, promoter opening and first phosphodiester bond formation and before elongation. We provide evidence to suggest that UBF activates transcription in the transition between initiation and elongation, at promoter escape by Pol I. This novel role for UBF in promoter escape would allow control of rRNA synthesis at active rDNA repeats, independent of and complementary to the promoter-specific targeting of SL1 and Pol I during PIC assembly. We posit that stimulation of promoter escape could be a general mechanism of activator function.
Panov
Kostya I
KI
Division of Gene Regulation and Expression, School of Life Sciences, Wellcome Trust Biocentre, University of Dundee, Dundee, UK.
Friedrich
J Karsten
JK
Russell
Jackie
J
Zomerdijk
Joost C B M
JC
D001483:Base Sequence; D004275:DNA, Ribosomal / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010441:Peptide Chain Elongation, Translational / Q000235:genetics; D010442:Peptide Chain Initiation, Translational / Q000235:genetics; D035463:Pol1 Transcription Initiation Complex Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012318:RNA Polymerase I / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*
D004275:DNA, Ribosomal; D035463:Pol1 Transcription Initiation Complex Proteins; C063844:transcription factor UBF; D012318:RNA Polymerase I