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Nature. 2014 Mar 13;507(7491):258-261. doi: 10.1038/nature12971. Epub 2014 Feb 16.

DNA-guided DNA interference by a prokaryotic Argonaute.

Author information

1
Laboratory of Microbiology, Department of Agrotechnology and Food Sciences, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, the Netherlands.
2
Clare Hall Laboratories, Cancer Research UK, London Research Institute, South Mimms EN6 3LD, UK.
3
Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
4
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
5
Centro de Biología Molecular Severo Ochoa, UAM-CSIC, Campus de Cantoblanco, 28049 Madrid, Spain.
#
Contributed equally

Abstract

RNA interference is widely distributed in eukaryotes and has a variety of functions, including antiviral defence and gene regulation. All RNA interference pathways use small single-stranded RNA (ssRNA) molecules that guide proteins of the Argonaute (Ago) family to complementary ssRNA targets: RNA-guided RNA interference. The role of prokaryotic Ago variants has remained elusive, although bioinformatics analysis has suggested their involvement in host defence. Here we demonstrate that Ago of the bacterium Thermus thermophilus (TtAgo) acts as a barrier for the uptake and propagation of foreign DNA. In vivo, TtAgo is loaded with 5'-phosphorylated DNA guides, 13-25 nucleotides in length, that are mostly plasmid derived and have a strong bias for a 5'-end deoxycytidine. These small interfering DNAs guide TtAgo to cleave complementary DNA strands. Hence, despite structural homology to its eukaryotic counterparts, TtAgo functions in host defence by DNA-guided DNA interference.

PMID:
24531762
PMCID:
PMC4697943
DOI:
10.1038/nature12971
[Indexed for MEDLINE]
Free PMC Article

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