Molecular basis of specific viral RNA recognition and 5'-end capping by the Chikungunya virus nsP1

Many viruses encode RNA-modifying enzymes to edit the 5' end of viral RNA to mimic the cellular mRNA for effective protein translation, genome replication, and evasion of the host defense mechanisms. Alphavirus nsP1 synthesizes the 5' end Cap-0 structure of viral RNAs. However, the molecul...

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Main Authors: Zhang, Kuo, Law, Michelle Cheok Yien, Nguyen, Trinh Mai, Tan, Yaw Bia, Wirawan, Melissa, Law, Yee-Song, Jeong, Lak Shin, Luo, Dahai
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/164882
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1648822023-02-28T17:14:17Z Molecular basis of specific viral RNA recognition and 5'-end capping by the Chikungunya virus nsP1 Zhang, Kuo Law, Michelle Cheok Yien Nguyen, Trinh Mai Tan, Yaw Bia Wirawan, Melissa Law, Yee-Song Jeong, Lak Shin Luo, Dahai Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences NTU Institute of Structural Biology Science::Medicine Science::Biological sciences mRNA Chikungunya Virus Many viruses encode RNA-modifying enzymes to edit the 5' end of viral RNA to mimic the cellular mRNA for effective protein translation, genome replication, and evasion of the host defense mechanisms. Alphavirus nsP1 synthesizes the 5' end Cap-0 structure of viral RNAs. However, the molecular basis of the capping process remains unclear. We determine high-resolution cryoelectron microscopy (cryo-EM) structures of Chikungunya virus nsP1 in complex with m7GTP/SAH, covalently attached m7GMP, and Cap-0 viral RNA. These structures reveal details of viral-RNA-capping reactions and uncover a sequence-specific virus RNA-recognition pattern that, in turn, regulates viral-RNA-capping efficiency to ensure optimal genome replication and subgenomic RNA transcription. This sequence-specific enzyme-RNA pairing is conserved across all alphaviruses. Ministry of Education (MOE) National Research Foundation (NRF) Published version This research is supported by the Singapore National Research Foundation grant NRF2016NRF-CRP001-063 and the Singapore Ministry of Education under its MOE AcRF Tier 2 Award MOE-T2EP30220-0009 and MOE AcRF Tier 1 Award 2021-T1-002-021 to D.L. 2023-02-22T01:40:17Z 2023-02-22T01:40:17Z 2022 Journal Article Zhang, K., Law, M. C. Y., Nguyen, T. M., Tan, Y. B., Wirawan, M., Law, Y., Jeong, L. S. & Luo, D. (2022). Molecular basis of specific viral RNA recognition and 5'-end capping by the Chikungunya virus nsP1. Cell Reports, 40(4), 111133-. https://dx.doi.org/10.1016/j.celrep.2022.111133 2211-1247 https://hdl.handle.net/10356/164882 10.1016/j.celrep.2022.111133 35905713 2-s2.0-85135073706 4 40 111133 en NRF2016NRF-CRP001-063 MOE-T2EP30220-0009 2021-T1-002-021 Cell Reports © 2022 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Science::Biological sciences
mRNA
Chikungunya Virus
spellingShingle Science::Medicine
Science::Biological sciences
mRNA
Chikungunya Virus
Zhang, Kuo
Law, Michelle Cheok Yien
Nguyen, Trinh Mai
Tan, Yaw Bia
Wirawan, Melissa
Law, Yee-Song
Jeong, Lak Shin
Luo, Dahai
Molecular basis of specific viral RNA recognition and 5'-end capping by the Chikungunya virus nsP1
description Many viruses encode RNA-modifying enzymes to edit the 5' end of viral RNA to mimic the cellular mRNA for effective protein translation, genome replication, and evasion of the host defense mechanisms. Alphavirus nsP1 synthesizes the 5' end Cap-0 structure of viral RNAs. However, the molecular basis of the capping process remains unclear. We determine high-resolution cryoelectron microscopy (cryo-EM) structures of Chikungunya virus nsP1 in complex with m7GTP/SAH, covalently attached m7GMP, and Cap-0 viral RNA. These structures reveal details of viral-RNA-capping reactions and uncover a sequence-specific virus RNA-recognition pattern that, in turn, regulates viral-RNA-capping efficiency to ensure optimal genome replication and subgenomic RNA transcription. This sequence-specific enzyme-RNA pairing is conserved across all alphaviruses.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Zhang, Kuo
Law, Michelle Cheok Yien
Nguyen, Trinh Mai
Tan, Yaw Bia
Wirawan, Melissa
Law, Yee-Song
Jeong, Lak Shin
Luo, Dahai
format Article
author Zhang, Kuo
Law, Michelle Cheok Yien
Nguyen, Trinh Mai
Tan, Yaw Bia
Wirawan, Melissa
Law, Yee-Song
Jeong, Lak Shin
Luo, Dahai
author_sort Zhang, Kuo
title Molecular basis of specific viral RNA recognition and 5'-end capping by the Chikungunya virus nsP1
title_short Molecular basis of specific viral RNA recognition and 5'-end capping by the Chikungunya virus nsP1
title_full Molecular basis of specific viral RNA recognition and 5'-end capping by the Chikungunya virus nsP1
title_fullStr Molecular basis of specific viral RNA recognition and 5'-end capping by the Chikungunya virus nsP1
title_full_unstemmed Molecular basis of specific viral RNA recognition and 5'-end capping by the Chikungunya virus nsP1
title_sort molecular basis of specific viral rna recognition and 5'-end capping by the chikungunya virus nsp1
publishDate 2023
url https://hdl.handle.net/10356/164882
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