한빛사논문
- 조회260
Carolien Bastiaanssen1,10, Pilar Bobadilla Ugarte2,10, Kijun Kim1,10, Giada Finocchio3,10, Yanlei Feng4,5,10, Todd A. Anzelon6, Stephan Köstlbacher7, Daniel Tamarit7,8, Thijs J. G. Ettema7, Martin Jinek3, Ian J. MacRae6, Chirlmin Joo1,9, Daan C. Swarts2 & Fabai Wu4
1Department of BioNanoScience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands.
2Laboratory of Biochemistry, Wageningen University, Wageningen, The Netherlands.
3Department of Biochemistry, University of Zurich, Zurich, Switzerland.
4School of Life Sciences, College of Science, Eastern Institute of Technology, Ningbo, China.
5Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, China.
6Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
7Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
8Theoretical Biology and Bioinformatics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
9Department of Physics, Ewha Womans University, Seoul, Korea.
10These authors contributed equally: Carolien Bastiaanssen, Pilar Bobadilla Ugarte, Kijun Kim, Giada Finocchio, Yanlei Feng.
Corresponding authors
Correspondence to Chirlmin Joo, Daan C. Swarts or Fabai Wu.
Abstract
Argonaute proteins are the central effectors of RNA-guided RNA silencing pathways in eukaryotes, playing crucial roles in gene repression and defense against viruses and transposons. Eukaryotic Argonautes are subdivided into two clades: AGOs generally facilitate miRNA- or siRNA-mediated silencing, while PIWIs generally facilitate piRNA-mediated silencing. It is currently unclear when and how Argonaute-based RNA silencing mechanisms arose and diverged during the emergence and early evolution of eukaryotes. Here, we show that in Asgard archaea, the closest prokaryotic relatives of eukaryotes, an evolutionary expansion of Argonaute proteins took place. In particular, a deep-branching PIWI protein (HrAgo1) encoded by the genome of the Lokiarchaeon ‘Candidatus Harpocratesius repetitus’ shares a common origin with eukaryotic PIWI proteins. Contrasting known prokaryotic Argonautes that use single-stranded DNA as guides and/or targets, HrAgo1 mediates RNA-guided RNA cleavage, and facilitates gene silencing when expressed in human cells and supplied with miRNA precursors. A cryo-EM structure of HrAgo1, combined with quantitative single-molecule experiments, reveals that the protein displays structural features and target-binding modes that are a mix of those of eukaryotic AGO and PIWI proteins. Thus, this deep-branching archaeal PIWI may have retained an ancestral molecular architecture that preceded the functional and mechanistic divergence of eukaryotic AGOs and PIWIs.
논문정보
- Research article
- 2024년 06월 (BRIC 등록일 2024-07-04)
- 국내(교신)+국외 연구진
- 생명과학 > 분자생물학
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