Journal News

How bacteria inhibit gene expression

Meric Ozturk
Dec. 5, 2023

Bacteria adapt to environmental changes by regulating their metabolism. The best way to do this is to change the gene expression. Proteins called transcription factors take care of this job and help organisms respond to change.

The transcription factor CarD is conserved among several bacterial lineages and reacts with other proteins to prevent or initiate gene expression. Although researchers know the initiating mechanism of CarD, they do not yet understand how it inhibits gene expression. Understanding the complete mechanism of CarD activity may help scientists develop new approaches to combat bacteria.

Dennis Zhu and Christina Stallings, researchers at the Washington University School of Medicine, study the inhibiting mechanism in Mycobacterium tuberculosis, or Mtb. They recently showed which factors affect CarD’s activity in gene expression.

The RNA polymerase, or RNAP, enzyme binds to DNA to promote transcription. RNAP binds a promoter sequence to start transcription, and the RNAP–promoter interaction is called RNAP-promoter open complex, or RPo. Previous studies showed that CarD stabilizes RPo and initiates RNAP’s activity. However, using RNA sequencing, Zhu and Stallings showed that altering the activity of CarD can cause downregulation and upregulation of some genes.

According to Zhu, their findings published in the Journal of Biological Chemistry are broadly applicable for other bacterial transcription factors as well.

“I believe what makes our study unique is that we approached it with a constrained hypothesis that the outcome of CarD regulation on mycobacterial transcription is dependent on RPo stability,” Zhu said. “Other studies of RNAP-binding transcription factors have explored the natural promoter space of a bacterium and have performed similar promoter bashing to identify regulatory sequences.”

Unlike previous studies, Zhu and Stallings observed the effect of CarD under different promoters. They showed that it has an inhibitory effect on promoters that already have highly stable RPo. This is the first demonstration of CarD’s transcriptional repression activity, and they believe that this is how CarD inhibits some genes.

The researchers did all these experiments in the controlled conditions of a laboratory. However, a bacteria’s natural environment is different. “The main limitation of studies like ours is the gap in understanding between the next-generation sequencing data sets that we gather from bacteria and the mechanistic details from our in test tube assays,” Zhu said. “So many things are happening within the bacterium such as salt conditions, other proteins, chromosome architecture, translation, which we cannot fully capture in an in vitro transcription assay.”

The next step for the group is creating a bridge between findings in the lab and more natural settings. CarD is a stress-response protein. That is, when bacteria feel environmental stress such as lack of nutrition or DNA damage, CarD is downregulated or upregulated, respectively.

Zhu and colleagues got bulk RNA sequencing data sets by exponentially growing Mycobacterium tuberculosis cells in a nutrient-rich media. “It would be interesting to explore how certain stress conditions, particularly nutrient starvation and DNA damage, affect CarD’s ability to regulate,” he said.

Enjoy reading ASBMB Today?

Become a member to receive the print edition monthly and the digital edition weekly.

Learn more
Meric Ozturk

Meric Ozturk is a Ph.D. student in biochemistry at Iowa State University and an ASBMB Today volunteer contributor.

Related articles

From the journals: JBC
Marissa Locke Rottinghaus
From the journals: JBC
Ken Farabaugh
From the journals: JBC
Isabel Casas
From the journals: JBC
Isabel Casas

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Seeking the sweet spot to beat a pig parasite
Journal News

Seeking the sweet spot to beat a pig parasite

July 16, 2024

Researchers extracted, separated and tested glycans from the porcine whipworm in an effort to determine the best way to develop treatments and vaccines.

Radioactive drugs strike cancer with precision
News

Radioactive drugs strike cancer with precision

July 14, 2024

The tumor-seeking radiopharmaceuticals are charting a new course in oncology, with promise for targeted treatments with fewer side effects.

Animals have used bioluminescence to communicate for millions of years
News

Animals have used bioluminescence to communicate for millions of years

July 13, 2024

Despite its widespread occurrence, scientists don’t yet know when or where this phenomenon first emerged, or its original function.

Getting to the genetic basis of cardiovascular disease
Journal News

Getting to the genetic basis of cardiovascular disease

July 11, 2024

Edwin G. Peña Martínez received a JBC Tabor award for associating the condition with mutations in noncoding sequences.

Microparticles safeguard vitamins and information
News

Microparticles safeguard vitamins and information

July 9, 2024

Scientists aim to use nanotechnology to combat malnutrition and improve medical recordkeeping in impoverished parts of the world.

Why AlphaFold 3 needs to be open source
Essay

Why AlphaFold 3 needs to be open source

July 7, 2024

The powerful AI-driven software from DeepMind was released without making its code openly available to scientists.