Genes are the basic element of living things, most of them carrying the information to make proteins from DNA through a process called ‘gene expression’. The basic elements of gene expression are two steps, called transcription and translation. In the transcription phase, machinery called RNA polymerase makes an RNA transcript of the gene. This transcript is then translated into a protein in the second step. A single bacterial cell has thousands of different genes encoding all of the proteins that a cell needs. Gene expression is often condition-dependent, in some cases being turned on or off, or increased or decreased, in response to environmental triggers.
Regulation of gene expression is an important field of study with critical implications. For example, the proteins that bacteria make to cause infection are often only made when it receives the right signal. Some bacteria can make molecules that may have antibacterial properties against other bacteria. With a better understanding of how gene expression is regulated, it may be possible to manipulate gene expression to treat infection or to harvest beneficial gene products. A recent review published in the Canadian Journal of Microbiology by Maria C. Davis, Christopher A Kesthely, Emily A. Franklin, and Shawn R. MacLellan at the University of New Brunswick describes recent structural and functional advances in our understanding of one of the master regulators of bacterial gene expression, the sigma factor.
Schematic of initiation of gene transcription. Source: Davis et al., The Essential Activities of the Basterial Sigma Factor, Canadian Journal of Microbiology
Sigma factors are members of a family of bacterial proteins called ‘transcription factors’. They work by interacting with the RNA polymerase, and targeting the entire assembly to the appropriate gene. When the gene is found, the double stranded DNA of the cell unwinds, allowing the machinery to access the single strand of DNA called the ‘template’. RNA polymerase then reads the template strand to make the gene transcript and the sigma factor is released from the machinery while the transcript grows and is eventually completed.
Sigma factors have a well-known role in targeting the RNA polymerase to specific genes. However, recent advances in our understanding of sigma factor function have shed more light on its other roles in transcription. This review from Davis et al. highlights two much less appreciated sigma factor functions: its ability to regulate gene expression by interacting with other transcription factors, and a mechanistic role in unwinding double stranded DNA.
Bacteria have multiple sigma factors that are each responsible for regulating different genes. To distinguish between genes, the sigma factors have to work as specificity factors, targeting RNA polymerase to specific genes so they can be expressed at the right time. Just like how two correctly matched puzzle pieces can fit each other just right, the structural elements in a sigma factor have to match the gene as well. To do this, the sigma factors recognize specific regions that precede the gene, called the -10 and -35 regions. Differences in these regions can determine whether or not they are compatible with a given sigma factor. Thus, a sigma factor can target the transcription machinery to specific genes or sets of genes.
In addition to sigma factors, bacteria have many other transcription factors that regulate gene expression at different parts of the transcription process. Some transcription activators can also directly interact with the sigma factor, promoting its association with the RNA polymerase. The most common method is by facilitating sigma factor targeting of -35 and -10 regions of target genes. Transcriptional activators can bend or twist the -35 and -10 regions to make them more accessible for the transcription machinery.
Negative transcriptional regulators decrease gene expression. Together with transcriptional activators, they allow the bacterium to fine-tune gene expression as the occasion calls for it. Bacteria can have anti-sigma factors that interact with the sigma factor and prevent it from interacting with the RNA polymerase. Sigma factors are implicated in large networks of regulation, having to respond to positive and negative regulators. The activity of these regulators can in turn be in response to different chemical or environmental signals. Ultimately, the interactions between sigma factors and the other transcription factors is what link a bacterium’s sensory system to gene expression.
The third function of sigma factors is to promote the opening of double stranded DNA so the transcription machinery can read the gene. When the fully assembled transcription machinery finds its gene, a small region immediately preceding the gene opens up. Structural studies suggest that the sigma factor has pockets on its surface to bind specific nucleotides in the non-template strand of DNA. The interaction between these nucleotides and the sigma factor locks the region into an ‘open’ single stranded form. Locking into the ‘open’ form precedes initiation of transcription, and is essential to the entire process.
Transcription—and gene expression as a whole—is a fundamental biological processes. Many of the recent advances in our understanding of sigma factor function have come from structural biology studies—being able to look at how sigma factors interact with other proteins and DNA at the molecular level. Continued studies of the processes involved in transcription can improve our understanding of how they occur not just in bacteria, but also in everything from viruses to humans as well. Davis et al. predict that further structural studies will continue to promote our understanding how transcription works at the atomic level.
Read the paper, “The Essential Activities of the Bacterial Sigma Factor” Maria C. Davis, Christopher A Kesthely, Emily A. Franklin, and Shawn R. MacLellan in the Canadian Journal of Microbiology.
