Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/153718
Title: Insights into the structure and RNA-binding specificity of Caenorhabditis elegans Dicer-related helicase 3 (DRH-3)
Authors: Li, Kuohan
Zheng, Jie
Wirawan, Melissa
Trinh, Nguyen Mai
Fedorova, Olga
Griffin, Patrick R.
Pyle, Anna M.
Luo, Dahai
Keywords: Science::Medicine
Science::Biological sciences
Issue Date: 2021
Source: Li, K., Zheng, J., Wirawan, M., Trinh, N. M., Fedorova, O., Griffin, P. R., Pyle, A. M. & Luo, D. (2021). Insights into the structure and RNA-binding specificity of Caenorhabditis elegans Dicer-related helicase 3 (DRH-3). Nucleic Acids Research, 49(17), 9978-9991. https://dx.doi.org/10.1093/nar/gkab712
Project: NMRC/OFIRG/0075/2018
2018-T1-002-010
Journal: Nucleic Acids Research
Abstract: DRH-3 is critically involved in germline development and RNA interference (RNAi) facilitated chromosome segregation via the 22G-siRNA pathway in Caenorhabditis elegans. DRH-3 has similar domain architecture to RIG-I-like receptors (RLRs) and belongs to the RIG-I-like RNA helicase family. The molecular understanding of DRH-3 and its function in endogenous RNAi pathways remains elusive. In this study, we solved the crystal structures of the DRH-3 N-terminal domain (NTD) and the C-terminal domains (CTDs) in complex with 5'-triphosphorylated RNAs. The NTD of DRH-3 adopts a distinct fold of tandem caspase activation and recruitment domains (CARDs) structurally similar to the CARDs of RIG-I and MDA5, suggesting a signaling function in the endogenous RNAi biogenesis. The CTD preferentially recognizes 5'-triphosphorylated double-stranded RNAs bearing the typical features of secondary siRNA transcripts. The full-length DRH-3 displays unique structural dynamics upon binding to RNA duplexes that differ from RIG-I or MDA5. These features of DRH-3 showcase the evolutionary divergence of the Dicer and RLR family of helicases.
URI: https://hdl.handle.net/10356/153718
ISSN: 0305-1048
DOI: 10.1093/nar/gkab712
Rights: © 2021 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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