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      DNA interference and beyond: structure and functions of prokaryotic Argonaute proteins

      review-article
      1 , 1 , 2 , , 1 ,
      Nature Communications
      Nature Publishing Group UK

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          Abstract

          Recognition and repression of RNA targets by Argonaute proteins guided by small RNAs is the essence of RNA interference in eukaryotes. Argonaute proteins with diverse structures are also found in many bacterial and archaeal genomes. Recent studies revealed that, similarly to their eukaryotic counterparts, prokaryotic Argonautes (pAgos) may function in cell defense against foreign genetic elements but, in contrast, preferably act on DNA targets. Many crucial details of the pAgo action, and the roles of a plethora of pAgos with non-conventional architecture remain unknown. Here, we review available structural and biochemical data on pAgos and discuss their possible functions in host defense and other genetic processes in prokaryotic cells.

          Abstract

          In this review, Aravin and colleagues examine bacterial and archaeal Argonaute proteins, discuss their diverse architectures and their possible roles in host defense, proposing additional functions for Argonaute proteins in prokaryotic cells.

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          Most cited references96

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          Small silencing RNAs: an expanding universe.

          Since the discovery in 1993 of the first small silencing RNA, a dizzying number of small RNA classes have been identified, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). These classes differ in their biogenesis, their modes of target regulation and in the biological pathways they regulate. There is a growing realization that, despite their differences, these distinct small RNA pathways are interconnected, and that small RNA pathways compete and collaborate as they regulate genes and protect the genome from external and internal threats.
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            RNA silencing in plants.

            There are at least three RNA silencing pathways for silencing specific genes in plants. In these pathways, silencing signals can be amplified and transmitted between cells, and may even be self-regulated by feedback mechanisms. Diverse biological roles of these pathways have been established, including defence against viruses, regulation of gene expression and the condensation of chromatin into heterochromatin. We are now in a good position to investigate the full extent of this functional diversity in genetic and epigenetic mechanisms of genome control.
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              Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs.

              Argonaute proteins associate with small RNAs that guide mRNA degradation, translational repression, or a combination of both. The human Argonaute family has eight members, four of which (Ago1 through Ago4) are closely related and coexpressed in many cell types. To understand the biological function of the different Ago proteins, we set out to determine if Ago1 through Ago4 are associated with miRNAs as well as RISC activity in human cell lines. Our results suggest that miRNAs are incorporated indiscriminately of their sequence into Ago1 through Ago4 containing microRNPs (miRNPs). Purification of the FLAG/HA-epitope-tagged Ago containing complexes from different human cell lines revealed that endonuclease activity is exclusively associated with Ago2. Exogenously introduced siRNAs also associate with Ago2 for guiding target RNA cleavage. The specific role of Ago2 in guiding target RNA cleavage was confirmed independently by siRNA-based depletion of individual Ago members in combination with a sensitive positive-readout reporter assay.
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                Author and article information

                Contributors
                aaa@caltech.edu
                akulb@img.ras.ru
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                4 December 2018
                4 December 2018
                2018
                : 9
                : 5165
                Affiliations
                [1 ]ISNI 0000 0001 2192 9124, GRID grid.4886.2, Institute of Molecular Genetics, , Russian Academy of Sciences, ; Moscow, 123182 Russia
                [2 ]ISNI 0000000107068890, GRID grid.20861.3d, Division of Biology and Biological Engineering, , California Institute of Technology, ; Pasadena, CA 91125 USA
                Article
                7449
                10.1038/s41467-018-07449-7
                6279821
                30514832
                efc2e2e2-c74c-4098-ab9a-843d0470cd54
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 2 February 2018
                : 26 October 2018
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