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Prokaryotic Transcriptional Activators and Repressors01:58

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The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Transcription Attenuation in Prokaryotes02:42

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Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Prokaryotes can control gene expression through operons—DNA sequences consisting of regulatory elements and clustered, functionally related protein-coding genes. Operons use a single promoter sequence to initiate transcription of a gene cluster (i.e., a group of structural genes) into a single mRNA molecule. The terminator sequence ends transcription. An operator sequence, located between the promoter and structural genes, prohibits the operon’s transcriptional activity if bound by...
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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Mycobacterium LacI-type Transcription Regulator Rv3575c Affects Host Innate Immunity by Regulating Bacterial mce4

Junfeng Zhen1, Yuerigu Abuliken1, Yaru Yan1

  • 1Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Chongqing 400715, China.

ACS Infectious Diseases
|September 5, 2024
PubMed
Summary

Mycobacterium tuberculosis uses host cholesterol for survival. Rv3575c regulates this process, impacting bacterial pathogenesis and host immune response.

Keywords:
Mycobacterium tuberculosisRv3575ccell wallcholesterolinnate immune responsemce4

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Immunology

Background:

  • Mycobacterium tuberculosis utilizes host cholesterol as a carbon source for survival within granulomas.
  • Cholesterol metabolism is crucial for M. tuberculosis pathogenesis, involving cell wall remodeling.
  • Regulatory mechanisms of cholesterol uptake and their impact on host-pathogen interactions are not fully understood.

Purpose of the Study:

  • To investigate the regulatory role of Rv3575c in M. tuberculosis cholesterol metabolism.
  • To elucidate the impact of Rv3575c on bacterial survival and host immune response.

Main Methods:

  • Investigated the transcriptional regulation of mce4 genes by Rv3575c in M. tuberculosis.
  • Utilized Mycobacterium smegmatis as a model organism to study the function of Rv3575c and its homologue MSMEG6044.
  • Assessed the impact of Rv3575c/MSMEG6044 on cholesterol utilization, cell wall properties, drug resistance, and host immune responses (pyroptosis, cytokine production).

Main Results:

  • Rv3575c negatively regulates mce4 gene transcription in M. tuberculosis.
  • Overexpression of Rv3575c in M. smegmatis impaired cholesterol utilization, activated host innate immunity, and triggered pyroptosis.
  • MSMEG6044 knockout in M. smegmatis enhanced cell wall hydrophobicity and permeability, increased ethambutol resistance, suppressed host immune response, and promoted bacterial survival in macrophages and mice.

Conclusions:

  • Rv3575c plays a significant role in mycobacterial pathogenesis.
  • Rv3575c is a key regulator of cholesterol transport and utilization in mycobacteria.
  • Modulation of Rv3575c affects bacterial fitness and host immune evasion strategies.