Structural basis for the recognition of guide RNA and target DNA heteroduplex by Argonaute

Argonaute proteins are key players in the gene silencing mechanisms mediated by small nucleic acids in all domains of life from bacteria to eukaryotes. However, little is known about the Argonaute protein that recognizes guide RNA/target DNA. Here, we determine the 2 Å crystal structure of Rhodobact...

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Main Authors:	Miyoshi, Tomohiro, Ito, Kosuke, Murakami, Ryo, Uchiumi, Toshio
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919518/

id	pubmed-4919518
recordtype	oai_dc
spelling	pubmed-49195182016-07-11 Structural basis for the recognition of guide RNA and target DNA heteroduplex by Argonaute Miyoshi, Tomohiro Ito, Kosuke Murakami, Ryo Uchiumi, Toshio Article Argonaute proteins are key players in the gene silencing mechanisms mediated by small nucleic acids in all domains of life from bacteria to eukaryotes. However, little is known about the Argonaute protein that recognizes guide RNA/target DNA. Here, we determine the 2 Å crystal structure of Rhodobacter sphaeroides Argonaute (RsAgo) in a complex with 18-nucleotide guide RNA and its complementary target DNA. The heteroduplex maintains Watson–Crick base-pairing even in the 3′-region of the guide RNA between the N-terminal and PIWI domains, suggesting a recognition mode by RsAgo for stable interaction with the target strand. In addition, the MID/PIWI interface of RsAgo has a system that specifically recognizes the 5′ base-U of the guide RNA, and the duplex-recognition loop of the PAZ domain is important for the DNA silencing activity. Furthermore, we show that Argonaute discriminates the nucleic acid type (RNA/DNA) by recognition of the duplex structure of the seed region. Nature Publishing Group 2016-06-21 /pmc/articles/PMC4919518/ /pubmed/27325485 http://dx.doi.org/10.1038/ncomms11846 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Miyoshi, Tomohiro Ito, Kosuke Murakami, Ryo Uchiumi, Toshio
spellingShingle	Miyoshi, Tomohiro Ito, Kosuke Murakami, Ryo Uchiumi, Toshio Structural basis for the recognition of guide RNA and target DNA heteroduplex by Argonaute
author_facet	Miyoshi, Tomohiro Ito, Kosuke Murakami, Ryo Uchiumi, Toshio
author_sort	Miyoshi, Tomohiro
title	Structural basis for the recognition of guide RNA and target DNA heteroduplex by Argonaute
title_short	Structural basis for the recognition of guide RNA and target DNA heteroduplex by Argonaute
title_full	Structural basis for the recognition of guide RNA and target DNA heteroduplex by Argonaute
title_fullStr	Structural basis for the recognition of guide RNA and target DNA heteroduplex by Argonaute
title_full_unstemmed	Structural basis for the recognition of guide RNA and target DNA heteroduplex by Argonaute
title_sort	structural basis for the recognition of guide rna and target dna heteroduplex by argonaute
description	Argonaute proteins are key players in the gene silencing mechanisms mediated by small nucleic acids in all domains of life from bacteria to eukaryotes. However, little is known about the Argonaute protein that recognizes guide RNA/target DNA. Here, we determine the 2 Å crystal structure of Rhodobacter sphaeroides Argonaute (RsAgo) in a complex with 18-nucleotide guide RNA and its complementary target DNA. The heteroduplex maintains Watson–Crick base-pairing even in the 3′-region of the guide RNA between the N-terminal and PIWI domains, suggesting a recognition mode by RsAgo for stable interaction with the target strand. In addition, the MID/PIWI interface of RsAgo has a system that specifically recognizes the 5′ base-U of the guide RNA, and the duplex-recognition loop of the PAZ domain is important for the DNA silencing activity. Furthermore, we show that Argonaute discriminates the nucleic acid type (RNA/DNA) by recognition of the duplex structure of the seed region.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919518/
_version_	1613599169465810944

Structural basis for the recognition of guide RNA and target DNA heteroduplex by Argonaute

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