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 (IP) 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.