hRRN3 is essential in the SL1-mediated recruitment of RNA Polymerase I to rRNA gene promoters.
A crucial step in transcription is the recruitment of RNA polymerase to promoters. In the transcription of human rRNA genes by RNA Polymerase I (Pol I), transcription factor SL1 has a role as the essential core promoter binding factor. Little is known about the mechanism by which Pol I is recruited. We provide evidence for an essential role for hRRN3, the human homologue of a yeast Pol I transcription factor, in this process. We find that whereas the bulk of human Pol I complexes (I alpha) are transcriptionally inactive, hRRN3 defines a distinct subpopulation of Pol I complexes (I beta) that supports specific initiation of transcription. Human RRN3 interacts directly with TAF(I)110 and TAF(I)63 of promoter-selectivity factor SL1. Blocking this connection prevents recruitment of Pol I beta to the rDNA promoter. Furthermore, hRRN3 can be found in transcriptionally autonomous Pol I holoenzyme complexes. We conclude that hRRN3 functions to recruit initiation-competent Pol I to rRNA gene promoters. The essential role for hRRN3 in linking Pol I to SL1 suggests a mechanism for growth control of Pol I transcription.
Division of Gene Regulation and Expression, School of Life Sciences, Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, UK.
G
G
Miller
K I
KI
Panov
J K
JK
Friedrich
L
L
Trinkle-Mulcahy
A I
AI
Lamond
J C
JC
Zomerdijk
D001665:Binding Sites; D002466:Cell Nucleolus / Q000201:enzymology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D020035:Holoenzymes / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D035463:Pol1 Transcription Initiation Complex Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012318:RNA Polymerase I / Q000145:classification / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D020035:Holoenzymes; D035463:Pol1 Transcription Initiation Complex Proteins; D012335:RNA, Ribosomal; C428423:RRN3 protein, human; D014157:Transcription Factors; C063844:transcription factor UBF; C063660:transcription initiation factor TIF-IB; D012318:RNA Polymerase I