Incomplete transcripts dominate the Mycobacterium tuberculosis transcriptome.
Xiangwu Ju1, Shuqi Li2, Ruby Froom2,3
1Laboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, NY, USA.
Nature
|February 28, 2024
Summary
Most Mycobacterium tuberculosis (Mtb) transcripts are incomplete due to RNA polymerase pausing, a key checkpoint for bacterial adaptation. This pausing mechanism, influenced by the σ-factor and transcription-translation coupling, offers potential therapeutic targets for tuberculosis.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Mycobacterium tuberculosis (Mtb) causes tuberculosis (TB), a significant global health issue.
- Mtb adapts to environmental changes by altering gene expression, but regulatory mechanisms are unclear.
Purpose of the Study:
- To investigate the mechanisms regulating Mtb transcription.
- To profile the Mtb transcriptome at high resolution.
Main Methods:
- Utilized a sequencing method to determine RNA molecule termini in bacterial cells.
- Analyzed Mtb transcriptome to identify transcript lengths and RNA polymerase activity.
Main Results:
- Most Mtb transcripts are incomplete, with 5' ends at start sites and 3' ends downstream.
- Short RNAs are linked to paused RNA polymerases (RNAPs), not premature termination.
- Mtb RNAP pausing depends on σ-factor binding.
- Translating ribosomes enhance transcription elongation, suggesting transcription-translation coupling.
Conclusions:
- The Mtb transcriptome is characterized by incomplete transcripts due to RNAP pausing.
- RNAP pausing acts as a crucial transcriptional checkpoint for Mtb adaptation.
- This pausing mechanism presents a potential target for novel TB therapeutics.
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