Publications by authors named "Jason Saba"

The genomes of human gut bacteria in the genus Bacteroides include numerous operons for biosynthesis of diverse capsular polysaccharides (CPSs). The first two genes of each CPS operon encode a locus-specific paralog of transcription elongation factor NusG (called UpxY), which enhances transcript elongation, and a UpxZ protein that inhibits noncognate UpxYs. This process, together with promoter inversions, ensures that a single CPS operon is transcribed in most cells.

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Article Synopsis
  • The biogenesis of RNA by RNA polymerase (RNAP) requires specific accessory factors for regulating various stages of transcription, with NusG-Spt5 being the only universally conserved factor across all life forms.
  • NusG-Spt5's evolution has enabled it to maintain important interactions with RNAP, influencing transcription processes by either reducing or increasing pausing during RNA elongation based on the strength of its binding.
  • Recent research has uncovered the functional diversity of NusG-Spt5 among different organisms, showing variations in their target selection and roles in regulating critical biological processes, such as the production of antibiotics and toxins.
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Human gut species encode numerous (eight or more) tightly regulated capsular polysaccharides (CPS). Specialized paralogs of the universal transcription elongation factor NusG, called UpxY (Y), and an anti-Y UpxZ (Z) are encoded by the first two genes of each CPS operon. The Y-Z regulators combine with promoter inversions to limit CPS transcription to a single operon in most cells.

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  • Single-cell genetic heterogeneity is a key aspect of microbial biology, but studying it has been challenging due to the lack of accessible methods.
  • The proposed method, called DoTA-seq, utilizes droplet microfluidics for high-throughput single-cell sequencing of specific genetic loci across various microbes.
  • DoTA-seq allows researchers to track antibiotic-resistance genes and plasmids in human and mouse gut microbiomes, providing a powerful tool for exploring microbial genetic diversity.
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Article Synopsis
  • Population heterogeneity helps bacteria adapt to unpredictable environments, particularly in the human gut.
  • The study highlights how variations in gene expression, specifically through promoter inversion, affect bacterial surface structures.
  • Researchers used single-cell sequencing and modeling to show that different bacterial populations tend to converge to similar states over time, providing insights for studying various microbes, including pathogens.
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Travis et al. (2020) reveal how Francisella tularensis uses stress-induced ppGpp to activate its virulent pathogenesis program by tethering an αCTD-DNA organizer (PigR) to a σ-organizing heterodimer (MglA-SspA), highlighting the remarkable diversity of transcriptional mechanisms in under-studied bacteria.

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Transcriptional pausing underlies regulation of cellular RNA biogenesis. A consensus pause sequence that acts on RNA polymerases (RNAPs) from bacteria to mammals halts RNAP in an elemental paused state from which longer-lived pauses can arise. Although the structural foundations of pauses prolonged by backtracking or nascent RNA hairpins are recognized, the fundamental mechanism of the elemental pause is less well-defined.

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NusG/RfaH/Spt5 transcription elongation factors are the only transcription regulators conserved across all life. Bacterial NusG regulates RNA polymerase (RNAP) elongation complexes (ECs) across most genes, enhancing elongation by suppressing RNAP backtracking and coordinating ρ-dependent termination and translation. The NusG paralog RfaH engages the EC only at operon polarity suppressor (ops) sites and suppresses both backtrack and hairpin-stabilized pausing.

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