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CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III

Author

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  • Elitza Deltcheva

    (The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Umeå University, S-90187 Umeå, Sweden
    Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria)

  • Krzysztof Chylinski

    (The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Umeå University, S-90187 Umeå, Sweden
    Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria)

  • Cynthia M. Sharma

    (ZINF Research Center for Infectious Diseases, University of Würzburg, D-97080 Würzburg, Germany)

  • Karine Gonzales

    (Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria)

  • Yanjie Chao

    (ZINF Research Center for Infectious Diseases, University of Würzburg, D-97080 Würzburg, Germany
    RNA Biology Group, Institute for Molecular Infection Biology, University of Würzburg, D-97080 Würzburg, Germany)

  • Zaid A. Pirzada

    (Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria)

  • Maria R. Eckert

    (Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria)

  • Jörg Vogel

    (ZINF Research Center for Infectious Diseases, University of Würzburg, D-97080 Würzburg, Germany
    RNA Biology Group, Institute for Molecular Infection Biology, University of Würzburg, D-97080 Würzburg, Germany)

  • Emmanuelle Charpentier

    (The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Umeå University, S-90187 Umeå, Sweden
    Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria)

Abstract

CRISPR/Cas systems constitute a widespread class of immunity systems that protect bacteria and archaea against phages and plasmids, and commonly use repeat/spacer-derived short crRNAs to silence foreign nucleic acids in a sequence-specific manner. Although the maturation of crRNAs represents a key event in CRISPR activation, the responsible endoribonucleases (CasE, Cas6, Csy4) are missing in many CRISPR/Cas subtypes. Here, differential RNA sequencing of the human pathogen Streptococcus pyogenes uncovered tracrRNA, a trans-encoded small RNA with 24-nucleotide complementarity to the repeat regions of crRNA precursor transcripts. We show that tracrRNA directs the maturation of crRNAs by the activities of the widely conserved endogenous RNase III and the CRISPR-associated Csn1 protein; all these components are essential to protect S. pyogenes against prophage-derived DNA. Our study reveals a novel pathway of small guide RNA maturation and the first example of a host factor (RNase III) required for bacterial RNA-mediated immunity against invaders.

Suggested Citation

  • Elitza Deltcheva & Krzysztof Chylinski & Cynthia M. Sharma & Karine Gonzales & Yanjie Chao & Zaid A. Pirzada & Maria R. Eckert & Jörg Vogel & Emmanuelle Charpentier, 2011. "CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III," Nature, Nature, vol. 471(7340), pages 602-607, March.
  • Handle: RePEc:nat:nature:v:471:y:2011:i:7340:d:10.1038_nature09886
    DOI: 10.1038/nature09886
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    Cited by:

    1. Yang Liu & Filipe Pinto & Xinyi Wan & Zhugen Yang & Shuguang Peng & Mengxi Li & Jonathan M. Cooper & Zhen Xie & Christopher E. French & Baojun Wang, 2022. "Reprogrammed tracrRNAs enable repurposing of RNAs as crRNAs and sequence-specific RNA biosensors," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Ulaganathan, Kandasamy & Goud, Sravanthi & Reddy, Madhavi & Kayalvili, Ulaganathan, 2017. "Genome engineering for breaking barriers in lignocellulosic bioethanol production," Renewable and Sustainable Energy Reviews, Elsevier, vol. 74(C), pages 1080-1107.
    3. Hu, Xiaojun & Rousseau, Ronald, 2016. "Scientific influence is not always visible: The phenomenon of under-cited influential publications," Journal of Informetrics, Elsevier, vol. 10(4), pages 1079-1091.
    4. Alicia Broto & Erika Gaspari & Samuel Miravet-Verde & Vitor A. P. Martins Santos & Mark Isalan, 2022. "A genetic toolkit and gene switches to limit Mycoplasma growth for biosafety applications," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Dalton T. Ham & Tyler S. Browne & Pooja N. Banglorewala & Tyler L. Wilson & Richard K. Michael & Gregory B. Gloor & David R. Edgell, 2023. "A generalizable Cas9/sgRNA prediction model using machine transfer learning with small high-quality datasets," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Daphne Collias & Elena Vialetto & Jiaqi Yu & Khoa Co & Éva d. H. Almási & Ann-Sophie Rüttiger & Tatjana Achmedov & Till Strowig & Chase L. Beisel, 2023. "Systematically attenuating DNA targeting enables CRISPR-driven editing in bacteria," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    7. Raed Ibraheim & Phillip W. L. Tai & Aamir Mir & Nida Javeed & Jiaming Wang & Tomás C. Rodríguez & Suk Namkung & Samantha Nelson & Eraj Shafiq Khokhar & Esther Mintzer & Stacy Maitland & Zexiang Chen &, 2021. "Self-inactivating, all-in-one AAV vectors for precision Cas9 genome editing via homology-directed repair in vivo," Nature Communications, Nature, vol. 12(1), pages 1-17, December.

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