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

Zhang，Kuo1,2,5; Law，Michelle Cheok Yien1,2; Nguyen，Trinh Mai1,2; Tan，Yaw Bia1,2; Wirawan，Melissa1,2; Law，Yee Song1,2; Jeong，Lak Shin4; Luo，Dahai1,2,3

2022-07-26

10.1016/j.celrep.2022.111133

Cell Reports   Impact Factor & Quartile

2211-1247

2211-1247

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.

5′ end cap-0 antiviral CP: Microbiology CP: Molecular biology mRNA RNA virus

SCI

English

Others

Ministry of Education - Singapore[2021-T1-002-021];Ministry of Education - Singapore[MOE-T2EP30220-0009];National Research Foundation Singapore[NRF2016NRF-CRP001-063];

Cell Biology

Cell Biology

WOS:000842366700004

CELL PRESS

2-s2.0-85135073706

Scopus

1.Lee Kong Chian School of Medicine,Nanyang Technological University,Singapore,EMB 03-07, 59 Nanyang Drive,636921,Singapore
2.NTU Institute of Structural Biology,Nanyang Technological University,Singapore,EMB 06-01, 59 Nanyang Drive,636921,Singapore
3.School of Biological Sciences,Nanyang Technological University,Singapore,60 Nanyang Drive,636921,Singapore
4.College of Pharmacy,Seoul National University,Seoul,South Korea
5.School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong,518055,China

Zhang，Kuo,Law，Michelle Cheok Yien,Nguyen，Trinh Mai,等. Molecular basis of specific viral RNA recognition and 5′-end capping by the Chikungunya virus nsP1[J]. Cell Reports,2022,40(4).

Zhang，Kuo.,Law，Michelle Cheok Yien.,Nguyen，Trinh Mai.,Tan，Yaw Bia.,Wirawan，Melissa.,...&Luo，Dahai.(2022).Molecular basis of specific viral RNA recognition and 5′-end capping by the Chikungunya virus nsP1.Cell Reports,40(4).

Zhang，Kuo,et al."Molecular basis of specific viral RNA recognition and 5′-end capping by the Chikungunya virus nsP1".Cell Reports 40.4(2022).