The σ Subunit-Remodeling Factors: An Emerging Paradigms of Transcription Regulation

Abstract

Transcription initiation is a key checkpoint and highly regulated step of gene expression. The sigma (σ) subunit of RNA polymerase (RNAP) controls all transcription initiation steps, from recognition of the −10/−35 promoter elements, upon formation of the closed promoter complex (RPc), to stabilization of the open promoter complex (RPo) and stimulation of the primary steps in RNA synthesis. The canonical mechanism to regulate σ activity upon transcription initiation relies on activators that recognize specific DNA motifs and recruit RNAP to promoters. This mini-review describes an emerging group of transcriptional regulators that form a complex with σ or/and RNAP prior to promoter binding, remodel the σ subunit conformation, and thus modify RNAP activity. Such strategy is widely used by bacteriophages to appropriate the host RNAP. Recent findings on RNAP-binding protein A (RbpA) from Mycobacterium tuberculosis and Crl from Escherichia coli suggest that activator-driven changes in σ conformation can be a widespread regulatory mechanism in bacteria.

BosR and PlzA reciprocally regulate RpoS function to sustain Borrelia burgdorferi in ticks and mammals

“…However, only a handful of RpoS-regulated genes identified by TBDCapSeq contain putative BosR boxes within their upstream regions (75); thus, it seems unlikely that DNA binding by BosR is a prerequisite for all of its modulatory functions. In other bacteria, factors designated sigma activators regulate promoter recognition by RNAPs, including RNAP-RpoS, without binding to specific DNA sequences (76,77). In E. coli, the RpoS-specific sigma activator Crl facilitates and stabilizes holoenzyme assembly by tethering RpoS to RNAP via the b' subunit clamp toe domain (76,78,79).…”

“…In other bacteria, factors designated sigma activators regulate promoter recognition by RNAPs, including RNAP-RpoS, without binding to specific DNA sequences (76,77). In E. coli, the RpoS-specific sigma activator Crl facilitates and stabilizes holoenzyme assembly by tethering RpoS to RNAP via the b' subunit clamp toe domain (76,78,79). Although structurally unrelated to Crl, BosR could be acting analogously by recruiting RNAP to RpoS-dependent promoters in addition to DNA binding.…”

“…In E . coli , the RpoS-specific σ activator Crl facilitates and stabilizes holoenzyme assembly by tethering RpoS to RNAP via the β′ subunit clamp toe domain ( 76 , 78 , 79 ). Although structurally unrelated to Crl, BosR could be acting analogously by recruiting RNAP to RpoS-dependent promoters.…”

Molecular dissection of RbpA-mediated regulation of fidaxomicin sensitivity in mycobacteria

“…RNAP β Sw3 is positioned near the template DNA -3 and -4 nucleotides, raising the possibility that RNAP β Sw3 could play a role in DNA template strand positioning (20). The RNAP β flap, which includes the flap tip helix that interacts with σ region 4, is important for positioning σ region 4 for interaction with the -35 element of the promoter (21) and represents a common binding interface for transcription factors that directly interact with σ (22,23). The RNAP β' lid separates the RNA/DNA hybrid as part of the RNA exit channel and is required for RPo stability and J o u r n a l P r e -p r o o f transcription in E. coli and Thermus aquaticus (24,25).…”

Single START-domain protein Mtsp17 is involved in transcriptional regulation in Mycobacterium smegmatis

“…Transcription in MSM is carried out by a multi-subunit RNA polymerase and one of 28 sigma subunits [ 15 ]. The sigma subunit ensures the transcription machinery to initiate transcription of particular genes [ 16 , 17 ]. Sigma factors are post-translationally regulated by a partner switching system (PSS) in which anti-sigma factors sequester the sigma factor from the transcription machinery and anti-sigma factor antagonists lift the repression of sigma factors [ 18 – 20 ].…”