New insights into the functions of transcription factors that bind the rna polymerase secondary channel

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Abstract

Transcription elongation is regulated at several different levels, including control by various accessory transcription elongation factors. A distinct group of these factors interacts with the RNA polymerase secondary channel, an opening at the enzyme surface that leads to its active center. Despite investigation for several years, the activities and in vivo roles of some of these factors remain obscure. Here, we review the recent progress in understanding the functions of the secondary channel binding factors in bacteria. In particular, we highlight the surprising role of global regulator DksA in fidelity of RNA synthesis and the resolution of RNA polymerase traffic jams by the Gre factor. These findings indicate a potential link between transcription fidelity and collisions of the transcription and replication machineries.

Figures

  • Figure 1. Secondary channel binding factors (SCBFs). (A) Structure of the transcription elongation complex [26] was superimposed with structure of the elongation complex with factor Gfh1 [27]. The RNAP core is represented as a partially transparent grey surface with nucleic acids shown as ribbons and active center Mg2+ ions as red spheres. Gfh1 bound in the secondary channel is shown as purple ribbons; (B) Aligned available structures of bacterial SCBFs. The long N-terminal coiled-coil domain protrudes through the secondary channel of RNAP (see panel B), while the C-terminal globular domain is thought to be responsible for binding to RNAP. Note that the coiled-coil domain of Rnk is shorter than those of the other SCBFs and is turned relative to the C-terminal domain; (C) The mode of functioning of Gre factors, and the hypothetical mode of action for other SCBFs. The Gre factor is bound to the active elongation complex but does not impose hydrolytic activity on it [28]. Upon backtracking or misincorporation, the Gre factor protrudes its coiled-coil domain through the secondary channel of RNAP, where it substitutes for the catalytic domain Trigger Loop (TL). This substitution switches off the slow TL-dependent phosphodiester bond hydrolysis and, instead, facilitates highly efficient Gre-dependent hydrolysis. After resolution of the backtracked complex through RNA cleavage, the elongation complex
  • Table 1. Secondary channel binding factors discussed in this review.

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Zenkin, N., & Yuzenkova, Y. (2015). New insights into the functions of transcription factors that bind the rna polymerase secondary channel. Biomolecules, 5(3), 1195–1209. https://doi.org/10.3390/biom5031195

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