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

• Published in: Cell reports (Cambridge) 2022-07, Vol.40 (4), p.111133-111133, Article 111133
• Main Authors: Zhang, Kuo, Law, Michelle Cheok Yien, Nguyen, Trinh Mai, Tan, Yaw Bia, Wirawan, Melissa, Law, Yee-Song, Jeong, Lak Shin, Luo, Dahai
• Format: Article
• Language: English
• Subjects: 5′ end cap-0; antiviral; CP: Microbiology; CP: Molecular biology; mRNA; RNA virus
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.111133

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. [Display omitted] •Multiple structures of CHIKV nsP1 during viral RNA 5′-cap formation are presented•Molecular basis of viral RNA 5′-end capping by nsP1 is elucidated•nsP1 recognizes the 5′-end A1U2 sequence viral RNA of preference•The conserved 5′-end A1U2 is essential for viral RNA replication Zhang et al. report the high-resolution structures of nsP1 in complex with m7GTP/SAH, m7GMP, and Cap0-viral RNA representing the key steps during viral RNA 5′-cap formation by cryo-EM. These structures elucidate the molecular basis of specific viral RNA 5′-end capping by the Chikungunya virus nsP1.