Incomplete transcripts dominate the Mycobacterium tuberculosis transcriptome
© 2024. The Author(s)..
Mycobacterium tuberculosis (Mtb) is a bacterial pathogen that causes tuberculosis (TB), an infectious disease that is responsible for major health and economic costs worldwide1. Mtb encounters diverse environments during its life cycle and responds to these changes largely by reprogramming its transcriptional output2. However, the mechanisms of Mtb transcription and how they are regulated remain poorly understood. Here we use a sequencing method that simultaneously determines both termini of individual RNA molecules in bacterial cells3 to profile the Mtb transcriptome at high resolution. Unexpectedly, we find that most Mtb transcripts are incomplete, with their 5' ends aligned at transcription start sites and 3' ends located 200-500 nucleotides downstream. We show that these short RNAs are mainly associated with paused RNA polymerases (RNAPs) rather than being products of premature termination. We further show that the high propensity of Mtb RNAP to pause early in transcription relies on the binding of the σ-factor. Finally, we show that a translating ribosome promotes transcription elongation, revealing a potential role for transcription-translation coupling in controlling Mtb gene expression. In sum, our findings depict a mycobacterial transcriptome that prominently features incomplete transcripts resulting from RNAP pausing. We propose that the pausing phase constitutes an important transcriptional checkpoint in Mtb that allows the bacterium to adapt to environmental changes and could be exploited for TB therapeutics.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:627 |
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| Enthalten in: |
Nature - 627(2024), 8003 vom: 29. März, Seite 424-430 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ju, Xiangwu [VerfasserIn] |
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| Links: |
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| Themen: |
DNA-Directed RNA Polymerases |
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| Anmerkungen: |
Date Completed 15.03.2024 Date Revised 22.03.2024 published: Print-Electronic UpdateOf: bioRxiv. 2023 Mar 11;:. - PMID 36945399 Citation Status MEDLINE |
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| doi: |
10.1038/s41586-024-07105-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369087941 |
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| 245 | 1 | 0 | |a Incomplete transcripts dominate the Mycobacterium tuberculosis transcriptome |
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| 500 | |a UpdateOf: bioRxiv. 2023 Mar 11;:. - PMID 36945399 | ||
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Mycobacterium tuberculosis (Mtb) is a bacterial pathogen that causes tuberculosis (TB), an infectious disease that is responsible for major health and economic costs worldwide1. Mtb encounters diverse environments during its life cycle and responds to these changes largely by reprogramming its transcriptional output2. However, the mechanisms of Mtb transcription and how they are regulated remain poorly understood. Here we use a sequencing method that simultaneously determines both termini of individual RNA molecules in bacterial cells3 to profile the Mtb transcriptome at high resolution. Unexpectedly, we find that most Mtb transcripts are incomplete, with their 5' ends aligned at transcription start sites and 3' ends located 200-500 nucleotides downstream. We show that these short RNAs are mainly associated with paused RNA polymerases (RNAPs) rather than being products of premature termination. We further show that the high propensity of Mtb RNAP to pause early in transcription relies on the binding of the σ-factor. Finally, we show that a translating ribosome promotes transcription elongation, revealing a potential role for transcription-translation coupling in controlling Mtb gene expression. In sum, our findings depict a mycobacterial transcriptome that prominently features incomplete transcripts resulting from RNAP pausing. We propose that the pausing phase constitutes an important transcriptional checkpoint in Mtb that allows the bacterium to adapt to environmental changes and could be exploited for TB therapeutics | ||
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| 700 | 1 | |a Wang, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Lilic, Mirjana |e verfasserin |4 aut | |
| 700 | 1 | |a Delbeau, Madeleine |e verfasserin |4 aut | |
| 700 | 1 | |a Campbell, Elizabeth A |e verfasserin |4 aut | |
| 700 | 1 | |a Rock, Jeremy M |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Shixin |e verfasserin |4 aut | |
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