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pAgo-induced DNA interference protects bacteria from invader DNA

Kuzmenko, Anton and Oguienko, Anastasiya and Esyunina, Daria and Yudin, Denis and Petrova, Mayya and Kudinova, Alina and Maslova, Olga and Ninova, Maria and Ryazansky, Sergei and Leach, David and Aravin, Alexei A. and Kulbachinskiy, Andrey (2020) pAgo-induced DNA interference protects bacteria from invader DNA. . (Unpublished)

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Members of the conserved Argonaute protein family use small RNA guides to find their mRNA targets to regulate gene expression and suppress mobile genetic elements in eukaryotes. Argonautes are also present in many bacterial and archaeal species 1-3. Unlike eukaryotic proteins, several studied prokaryotic Argonautes use small DNA guides to cleave DNA, a process dubbed DNA interference 4-8. However, the natural functions and targets of DNA interference are poorly understood and the mechanisms of DNA guide generation and target discrimination remain unknown. Here, we studied the in vivo activities of a bacterial Argonaute nuclease CbAgo and demonstrated that it induces cleavage of multicopy genetic elements, including plasmids, transposons and repetitive chromosomal loci. Generation of small DNA guides employed by CbAgo requires cooperation between its intrinsic endonuclease activity and the cellular double-strand break repair machinery. The mechanism of guide generation ensures that small DNA guides are enriched in sequences that target foreign DNA and endows CbAgo with capacity to eliminate plasmids and fight phage infection. Similar principles may underlie the specificity of self-nonself discrimination by diverse defense systems in prokaryotes.

Item Type:Report or Paper (Discussion Paper)
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URLURL TypeDescription Paper
Ninova, Maria0000-0001-5051-5502
Ryazansky, Sergei0000-0002-3171-2997
Kulbachinskiy, Andrey0000-0002-2292-6424
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. Posted March 03, 2020. We thank Dr. Martin A. White for strains with engineered I-SceI sites, Dr. Gerry Smith for RecBCD antibodies. The project was in part supported by the Ministry of Science and Higher Education of the Russian Federation (14.W03.31.0007), Russian Science Foundation (19-14-00359), Russian Foundation for Basic Research (18-29-07086). DL is supported by grant MR/M019160/1 from the MRC (UK). Data and Code Availability: All data generated during this study are included in the published article and the Extended Data and are available from public databases. The codes used for data analysis are available from the corresponding authors upon reasonable request.
Funding AgencyGrant Number
Ministry of Education and Science of the Russian Federation14.W03.31.0007
Russian Science Foundation19-14-00359
Russian Foundation for Basic Research18-29-07086
Medical Research Council (UK)MR/M019160/1
Record Number:CaltechAUTHORS:20200304-081912707
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Official Citation:pAgo-induced DNA interference protects bacteria from invader DNA. Anton Kuzmenko, Anastasiya Oguienko, Daria Esyunina, Denis Yudin, Mayya Petrova, Alina Kudinova, Olga Maslova, Maria Ninova, Sergei Ryazansky, David Leach, Alexei A. Aravin, Andrey Kulbachinskiy. bioRxiv 2020.03.01.971358; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:101694
Deposited By: Tony Diaz
Deposited On:04 Mar 2020 18:49
Last Modified:04 Mar 2020 18:49

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