# Cooperative clamp-mediated promoter recognition by poxviral RNA polymerase and its TBP/TFIIB-like partner

## TL;DR

This study reveals how a poxvirus uses a unique protein pair to help its RNA polymerase recognize gene promoters for transcription.

## Contribution

The study identifies VITF-3 as an atypical TBP/TFIIB pair and shows its cooperative interaction with viral RNA polymerase for promoter recognition.

## Key findings

- VITF-3 forms a stable ring structure that requires viral RNA polymerase for promoter recognition.
- Cryo-EM analysis shows the viral RNA polymerase acts as a clamp loader for VITF-3.
- The complex anchors the polymerase at the transcription start site during promoter recognition.

## Abstract

The recruitment of RNA polymerase to gene promoters is a critical step in gene expression. For RNA polymerase II, this process is initiated by TBP and TFIIB, with homologs of these TBP/TFIIB pairs found in all known multi-subunit RNA polymerase systems. Here, we describe a mode of promoter recognition by the poxviral intermediate transcription factor 3, VITF-3. This heterodimeric factor comprises an atypical TBP/TFIIB pair forming a stable ring structure inert towards DNA in the absence of viral RNA polymerase. Promoter recognition instead requires concerted VITF-3 and viral RNA polymerase binding, as shown by cryo-EM analysis of the intermediate pre-initiation complex. During the formation of this complex, viral RNA polymerase facilitates ring opening and loading of VITF-3 onto the promoter, anchoring the polymerase at the transcription start site. Our findings suggest viral RNA polymerase could act as a clamp loader for VITF-3 and identify VITF-3 as an unusual TBP/TFIIB pair.

The recruitment of RNAPII to gene promoters is initiated by TBP and TFIIB. Here, the authors use cryo-EM to show how the RNAP from the Vaccinia virus recognizes promoters, identifying transcription factor VITF-3 as an atypical TBP/TFIIB pair.