TFIIB-related factors in RNA polymerase I transcription

Abstract

Eukaryotic RNA polymerases (Pol) I, II, III and archaeal Pol use a related set of general transcription factors to recognize promoter sequences, recruit Pol to promoters and to function at key points in the transcription initiation mechanism. The TFIIB-like general transcription factors (GTFs) function during several important and conserved steps in the initiation pathway for Pol II, III, and archaeal Pol. Until recently, the mechanism of Pol I initiation seemed unique, since it appeared to lack a GTF paralogous to the TFIIB-like proteins. The surprising recent discovery of TFIIB-related Pol I general factors in yeast and humans highlights the evolutionary conservation of transcription initiation mechanisms for all eukaryotic and archaeal Pols. These findings reveal new roles for the function of the Pol I GTFs and insight into the function of TFIIB-related factors. Models for Pol I transcription initiation are reexamined in light of these recent findings.

Structural insights into transcription initiation by yeast RNA polymerase I

“…Moreover, the cyclin domains of Rrn7 are positioned differently than TFIIB, while the Zn‐ribbon is present in a conserved position next to the RNA exit channel. This suggests that the N‐terminal region of Rrn7 might function in a similar manner to TFIIB, as proposed previously (Knutson & Hahn, 2013), but that the cyclin domains could have different or additional functions compared to the Pol II system although they use similar interfaces as TFIIB and Brf2 to interact with promoter DNA.…”

RNA Polymerase III Accurately Initiates Transcription from RNA Polymerase II Promoters in Vitro

“…Likewise, the transcription initiation factors for Pol I and Pol III (SL1/Tif-1B and TFIIIB, respectively) contain a TFIIB-related protein and TBP (or a TBP-related protein (Trf1) in Drosophila) counterparts (7)(8)(9)20).…”

Breaking the mold: structures of the RNA polymerase I transcription complex reveal a new path for initiation

“…Transcription initiation can be subdivided into the formation of a pre-initiation complex (PIC), closed complex (CC), open complex (OC), and initially transcribing complex (ITC) [6]. Efficient transcription of rDNA by Pol I relies on the recruitment of transcription factors to form the PIC that includes upstream activating factor (UAF), CF, TATA-box binding protein (TBP) and Rrn3 [2,7]. Once formed, the PIC transitions into the early initiation phases starting with the CC where the rDNA is double stranded to the OC where DNA near the transcription start site is melted, and finally the ITC where nascent RNA is first synthesized before entering the elongation phase [6,8].…”

“…The rDNA promoter region is bipartite comprising an upstream activation sequence and core element in which UAF and CF bind, respectively [2,7]. Collectively, recent structures demonstrate that CF primarily engages the rDNA promoter via two subunits Rrn7 and Rrn11, while Rrn6 has more of a scaffolding role in assembly of the complex and the PIC [3–5].…”

“…It will be exciting to see if these features are conserved in the human Pol I PIC and if the Rrn7 human ortholog, TAF1B of the SL1 complex, retains similar recruitment and post-recruitment properties in transcription initiation [10,32]. It is also noteworthy that TAF1B contains a large insertion within the N-terminal cyclin domain that is rich in modifiable residues that could possibly serve as a regulatory protein-protein interaction surface or have additional functions in SL1 recruitment, DNA engagement, or polymerase interaction given its placement within the structure [7,10]. We are hopeful that these new structures will help mold new strategies to specifically target the Pol I transcription machinery that is often upregulated in cancer [33–35].…”