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

Elitza Deltcheva, Krzysztof Chylinski, Cynthia M. Sharma, Karine Gonzales, Yanjie Chao, Zaid A. Pirzada, Maria R. Eckert, Jörg Vogel and Emmanuelle Charpentier ()
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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
Krzysztof Chylinski: The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Umeå University, S-90187 Umeå, Sweden
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
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
Emmanuelle Charpentier: The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Umeå University, S-90187 Umeå, Sweden

Nature, 2011, vol. 471, issue 7340, 602-607

Abstract: 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.

Date: 2011
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DOI: 10.1038/nature09886

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