1. Molecular basis of specific viral RNA recognition and 5'-end capping by the Chikungunya virus nsP1
- Author
-
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, and NTU Institute of Structural Biology
- Subjects
RNA Caps ,Chikungunya Virus ,mRNA ,Cryoelectron Microscopy ,Biological sciences [Science] ,RNA, Viral ,Medicine [Science] ,Viral Nonstructural Proteins ,Virus Replication ,Chikungunya virus ,General Biochemistry, Genetics and Molecular Biology - Abstract
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.
- Published
- 2021