This week in my Molecular class we discussed the role of sigma (σ) factors in regulating transcription. Sigma factors are proteins which bind to the DNA-Dependent RNA polymerase and mediate that enzyme’s binding to the promoters of prokaryotic genes. In this way, we can consider the core polymerase enzyme to be agnostic to which genes are transcribed, it is only the mediation of the sigma factor that guides the polymerase to one gene or another.
Under resting conditions, σ70 is expressed highly and guides the polymerase to constitutively express ‘normal’, housekeeping genes. However, under conditions of stress, such as heat shock, another sigma factor, σ24, becomes active, leading to the transcription (and subsequent translation) of a third factor, σ32. This third sigma factor then leads the polymerase to translate a number of heat shock response proteins such as chaparones, which help prevent protein denaturation and aggregation.
The question is, how does σ24 know when to become active and initiate this heat shock cascade?
Before answering this, we should ask ourselves what to expect.
How can a cell respond to heat shock before the heat shock proteins are made? The answer must be that somehow the heat shock itself leads to a difference in the sigma factors being utilized. I speculated in class that one possible mechanism would be that either the polymerase or σ24 might partially denature in a way that their association was favored over that of the polymerase and σ70.
Although that could work, it turns out not to be the case.
Boldrin et al. examine this question in the bacteria Mycobacterium tuberculosis and suggest that an anti-sigma factor, regulator of sigma E factor A (RseA), binds σ24 (which they call σE – however, I will continue calling it σ24 for consistency) and sequesters it under resting conditions. They continue, “[i]f [RseA] acted as a σ24-specific anti-sigma factor, we would expect to detect an upregulation of those genes whose expression is regulated by σ24 when [RseA] is absent.” One such gene regulated by σ24 is sigB. Conversely, if σ24 is knocked out, or if RseE is overexpressed, we would expect genes such as sigB to be repressed.
To demonstrate that σ24 does regulate sigB, cells missing σ24 were generated. Indeed, the expression of sigB was repressed about 10 times in these cells compared to the wild type (Figure 4). Similarly, when RseA was overexpressed, sigB was also repressed(Figure 5). Genes not regulated by σ24 were unaffected by the deletion of σ24 or the overexpression of RseA (data not shown)
Taken together these data indicate that the absence of RseA specifically increases the activity of σ24.
De Las Peñas et al. confirm that RseA is predicted to be an inner membrane protein, and the purified cytoplasmic domain binds to and inhibits σ24.
Of course the rabbit hole continues to deepen as we ask how RseA knows to release . It turns out that (cellular) envelope stress promotes RseA degradation, which occurs by a proteolytic cascade initiated by DegS, but that’s as far as we’ll go here. I hope this helps!
Assessing the role of Rv1222 (RseA) as an anti-sigma factor of the Mycobacterium tuberculosis extracytoplasmic sigma factor SigE Francesca Boldrin, Laura Cioetto Mazzabò, Saber Anoosheh, Giorgio Palù, Luc Gaudreau, Riccardo Manganelli & Roberta Provvedi Scientific Reports volume 9, Article number: 4513 (2019)
The σE‐mediated response to extracytoplasmic stress in Escherichia coli is transduced by RseA and RseB, two negative regulators of σE Alejandro De Las Peñas, Lynn Connolly, and Carol A. Gross 31 October 2003
The Single Extracytoplasmic-Function Sigma Factor of Xylella fastidiosa Is Involved in the Heat Shock Response and Presents an Unusual Regulatory Mechanism José F. da Silva Neto, Tie Koide, Suely L. Gomes, Marilis V. Marques Journal of Bacteriology Dec 2006, 189 (2) 551-560
January 25, 2020 at 11:17 am
Jack, this is Amanda Miller, you probably don’t remember me, I took all of your science classes at fscc. Any way, question…the coronavirus: with the start of symptoms are closely related to the common cold, if it sets up into the lungs enough to form pneumonia can that viral infection become bacterial or would it remain viral? And if it is truly viral and mimics closely to the same as the common cold, what is the likely hood of a vaccine? I thought I remembered that we do not have a vaccine for the common cold because of to many causing factors, unlike the flu which is bacterial. I look forward to your response!! And thank you in advance!
On Fri, Oct 18, 2019, 10:39 AM DownHouseSoftware wrote:
> downhousesoftware posted: “This week in my Molecular class we discussed > the role of sigma (σ) factors in regulating transcription. Sigma factors > are proteins which bind to the DNA-Dependent RNA polymerase and mediate > that enzyme’s binding to the promoters of prokaryotic genes. In t” >
October 11, 2020 at 8:58 am
Sure, I remember you! Good questions! The reason we don’t have a vaccine for colds is that there are many different viruses that all cause the same symptoms, so we call it the same thing. With SARS-CoV2, we have one agent causing illness, so that won’t pose the same problem – however, there is a decent amount of evidence that immunity to SARS-CoV2 is short-lived, which does present an obstacle to generating an effective, lasting vaccine.
Although there is a bacteria called Haemophilus influenzae, this is not what we regularly call the flu. Flu is viral, but it can predispose someone to an additional bacterial infection as a consequence of its symptoms. I imagine that SARS-CoV2 could do the same.
I hope this helps – It’s good to hear from you!