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Mycobacterial HelD connects RNA polymerase recycling with transcription initiation

Author

Listed:
  • Tomáš Kovaľ

    (Institute of Biotechnology of the Czech Academy of Sciences)

  • Nabajyoti Borah

    (Institute of Microbiology of the Czech Academy of Sciences
    Charles University)

  • Petra Sudzinová

    (Institute of Microbiology of the Czech Academy of Sciences)

  • Barbora Brezovská

    (Institute of Microbiology of the Czech Academy of Sciences)

  • Hana Šanderová

    (Institute of Microbiology of the Czech Academy of Sciences)

  • Viola Vaňková Hausnerová

    (Institute of Microbiology of the Czech Academy of Sciences
    Charles University)

  • Alena Křenková

    (Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences)

  • Martin Hubálek

    (Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences)

  • Mária Trundová

    (Institute of Biotechnology of the Czech Academy of Sciences)

  • Kristýna Adámková

    (Institute of Biotechnology of the Czech Academy of Sciences)

  • Jarmila Dušková

    (Institute of Biotechnology of the Czech Academy of Sciences)

  • Marek Schwarz

    (Institute of Microbiology of the Czech Academy of Sciences)

  • Jana Wiedermannová

    (Institute of Microbiology of the Czech Academy of Sciences)

  • Jan Dohnálek

    (Institute of Biotechnology of the Czech Academy of Sciences)

  • Libor Krásný

    (Institute of Microbiology of the Czech Academy of Sciences)

  • Tomáš Kouba

    (Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences)

Abstract

Mycobacterial HelD is a transcription factor that recycles stalled RNAP by dissociating it from nucleic acids and, if present, from the antibiotic rifampicin. The rescued RNAP, however, must disengage from HelD to participate in subsequent rounds of transcription. The mechanism of release is unknown. We show that HelD from Mycobacterium smegmatis forms a complex with RNAP associated with the primary sigma factor σA and transcription factor RbpA but not CarD. We solve several structures of RNAP-σA-RbpA-HelD without and with promoter DNA. These snapshots capture HelD during transcription initiation, describing mechanistic aspects of HelD release from RNAP and its protective effect against rifampicin. Biochemical evidence supports these findings, defines the role of ATP binding and hydrolysis by HelD in the process, and confirms the rifampicin-protective effect of HelD. Collectively, these results show that when HelD is present during transcription initiation, the process is protected from rifampicin until the last possible moment.

Suggested Citation

  • Tomáš Kovaľ & Nabajyoti Borah & Petra Sudzinová & Barbora Brezovská & Hana Šanderová & Viola Vaňková Hausnerová & Alena Křenková & Martin Hubálek & Mária Trundová & Kristýna Adámková & Jarmila Dušková, 2024. "Mycobacterial HelD connects RNA polymerase recycling with transcription initiation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52891-5
    DOI: 10.1038/s41467-024-52891-5
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    References listed on IDEAS

    as
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