Regulation of Bacterial Gene Expression by Transcription Attenuation

Abstract

SUMMARY A wide variety of mechanisms that control gene expression in bacteria are based on conditional transcription termination. Generally, in these mechanisms, a transcription terminator is located between a promoter and a downstream gene(s), and the efficiency of the terminator is controlled by a regulatory effector that can be a metabolite, protein, or RNA. The most common type of regulation involving conditional termination is transcription attenuation, in which the primary regulatory target is an essential element of a single terminator. The terminator can be either intrinsic or Rho dependent, with each presenting unique regulatory targets. Transcription attenuation mechanisms can be divided into five classes based primarily on the manner in which transcription termination is rendered conditional. This review summarizes each class of control mechanisms from a historical perspective, describes important examples in a physiological context and the current state of knowledge, highlights major advances, and discusses expectations of future discoveries.

Polycysteine-encoding leaderless short ORFs function as cysteine-responsive attenuators of operonic gene expression in mycobacteria

“…Ms5788A and peri-Shine-Dalgarno nucleotide changes in this series resulted in an 202 expression pattern similar to that of the wild-type construct, consistent with the model 203 Classical models of ribosome-mediated attenuation invoke competing mRNA stem loops 208 that form an intrinsic terminator structure when ribosomes rapidly translate the sORF, 209 resulting in regulation at the level of transcription (Yanofsky 1981;Turnbough 2019). In 210 the case of Ms5788 attenuation, regulation appears to occur at the level of translation.…”

“…Attenuation occurs when 89 abundant charged tRNA levels allow translating ribosomes to quickly clear the 90 modulating uORF, promoting the formation of an intrinsic terminator that aborts 91 transcription of the operon. Low levels of charged tRNA cause ribosome stalling in the 92 uORF at codons for the end-product amino acid, facilitating the formation of a competing 93 anti-terminator structure, thereby releasing attenuation to allow transcription to extend 94 into the biosynthetic operon (Turnbough 2019). uORF-mediated attenuation mechanisms 95 for cysteine have not been described.…”

NusG, an Ancient Yet Rapidly Evolving Transcription Factor

“…When the coupling is broken, e.g., by the ribosome pausing or stalling, Rho releases the nascent RNA, a phenomenon known as polarity ( Richardson, 1991 ). Transcription attenuation is another regulatory mechanism dependent on coupling between the RNAP and the trailing ribosome, wherein the formation of an RNA hairpin induces RNAP pausing and the trailing ribosome pushes the RNAP out of the pause ( Turnbough, 2019 ). By stabilizing the RNAP-ribosome tandem or aiding Rho, NusG controls the fate of the nascent RNA, promoting its translation or release.…”

Non-genetic inheritance restraint of cell-to-cell variation

“…While genetic information passed from generation to the next is the main scheme, by which cells conserve their characteristics, non-genetic cellular components, such as all proteins, RNA, and other chemicals, are also transferred between consecutive generations and thus influence the state of the cell’s characteristics (or its phenotype) in future generations ( Lambert et al, 2014 ; Robert et al, 2010 ). The mechanism of genetic information transfer between generations, as well as how this information is expressed, is mostly understood ( Casadesús and Low, 2006 ; Chen et al, 2017 ; Turnbough, 2019 ). This information can be altered by rare occurring processes such as mutations, lateral gene transfer, or gene loss ( Bryant et al, 2012 ; Robert et al, 2018 ).…”