Distinct RNA elements confer specificity to flavivirus RNA cap methylation events

Hongping Dong, Debashish Ray, Suping Ren, Bo Zhang, Francese Puig-Basagoiti, Yuko Takagi, C. Kiong Ho, Hongmin Li, Pei-Yong Shi

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

The 5′ end of the flavivirus plus-sense RNA genome contains a type 1 cap (m7GpppAniG), followed by a conserved stem-loop structure. We report that nonstructural protein 5 (NS5) from four serocomplexes of flaviviruses specifically methylates the cap through recognition of the 5′ terminus of viral RNA. Distinct RNA elements are required for the methylations at guanine N-7 on the cap and ribose 2′-OH on the first transcribed nucleotide. In a West Nile virus (WNV) model, N-7 cap methylation requires specific nucleotides at the second and third positions and a 5′ stem-loop structure; in contrast, 2′-OH ribose methylation requires specific nucleotides at the first and second positions, with a minimum 5′ viral RNA of 20 nucleotides. The cap analogues GpppA and m7GpppA are not active substrates for WNV methytransferase. Footprinting experiments using Gppp- and m7Gppp-terminated RNAs suggest that the 5′ termini of RNA substrates interact with NS5 during the sequential methylation reactions. Cap methylations could be inhibited by an antisense oligomer targeting the first 20 nucleotides of WNV genome. The viral RNA-specific cap methylation suggests methyltransferase as a novel target for flavivirus drug discovery.

Original languageEnglish (US)
Pages (from-to)4412-4421
Number of pages10
JournalJournal of Virology
Volume81
Issue number9
DOIs
StatePublished - May 2007
Externally publishedYes

Fingerprint

RNA Caps
Flavivirus
methylation
Methylation
RNA
Nucleotides
West Nile virus
Viral RNA
nucleotides
Ribose
ribose
Genome
Flaviviridae
Guanine
Methyltransferases
Drug Discovery
stems
genome
guanine
methyltransferases

ASJC Scopus subject areas

  • Immunology

Cite this

Distinct RNA elements confer specificity to flavivirus RNA cap methylation events. / Dong, Hongping; Ray, Debashish; Ren, Suping; Zhang, Bo; Puig-Basagoiti, Francese; Takagi, Yuko; Ho, C. Kiong; Li, Hongmin; Shi, Pei-Yong.

In: Journal of Virology, Vol. 81, No. 9, 05.2007, p. 4412-4421.

Research output: Contribution to journalArticle

Dong, H, Ray, D, Ren, S, Zhang, B, Puig-Basagoiti, F, Takagi, Y, Ho, CK, Li, H & Shi, P-Y 2007, 'Distinct RNA elements confer specificity to flavivirus RNA cap methylation events', Journal of Virology, vol. 81, no. 9, pp. 4412-4421. https://doi.org/10.1128/JVI.02455-06
Dong H, Ray D, Ren S, Zhang B, Puig-Basagoiti F, Takagi Y et al. Distinct RNA elements confer specificity to flavivirus RNA cap methylation events. Journal of Virology. 2007 May;81(9):4412-4421. https://doi.org/10.1128/JVI.02455-06
Dong, Hongping ; Ray, Debashish ; Ren, Suping ; Zhang, Bo ; Puig-Basagoiti, Francese ; Takagi, Yuko ; Ho, C. Kiong ; Li, Hongmin ; Shi, Pei-Yong. / Distinct RNA elements confer specificity to flavivirus RNA cap methylation events. In: Journal of Virology. 2007 ; Vol. 81, No. 9. pp. 4412-4421.
@article{ced02a3bcbe44e51b17d02c26f797090,
title = "Distinct RNA elements confer specificity to flavivirus RNA cap methylation events",
abstract = "The 5′ end of the flavivirus plus-sense RNA genome contains a type 1 cap (m7GpppAniG), followed by a conserved stem-loop structure. We report that nonstructural protein 5 (NS5) from four serocomplexes of flaviviruses specifically methylates the cap through recognition of the 5′ terminus of viral RNA. Distinct RNA elements are required for the methylations at guanine N-7 on the cap and ribose 2′-OH on the first transcribed nucleotide. In a West Nile virus (WNV) model, N-7 cap methylation requires specific nucleotides at the second and third positions and a 5′ stem-loop structure; in contrast, 2′-OH ribose methylation requires specific nucleotides at the first and second positions, with a minimum 5′ viral RNA of 20 nucleotides. The cap analogues GpppA and m7GpppA are not active substrates for WNV methytransferase. Footprinting experiments using Gppp- and m7Gppp-terminated RNAs suggest that the 5′ termini of RNA substrates interact with NS5 during the sequential methylation reactions. Cap methylations could be inhibited by an antisense oligomer targeting the first 20 nucleotides of WNV genome. The viral RNA-specific cap methylation suggests methyltransferase as a novel target for flavivirus drug discovery.",
author = "Hongping Dong and Debashish Ray and Suping Ren and Bo Zhang and Francese Puig-Basagoiti and Yuko Takagi and Ho, {C. Kiong} and Hongmin Li and Pei-Yong Shi",
year = "2007",
month = "5",
doi = "10.1128/JVI.02455-06",
language = "English (US)",
volume = "81",
pages = "4412--4421",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "9",

}

TY - JOUR

T1 - Distinct RNA elements confer specificity to flavivirus RNA cap methylation events

AU - Dong, Hongping

AU - Ray, Debashish

AU - Ren, Suping

AU - Zhang, Bo

AU - Puig-Basagoiti, Francese

AU - Takagi, Yuko

AU - Ho, C. Kiong

AU - Li, Hongmin

AU - Shi, Pei-Yong

PY - 2007/5

Y1 - 2007/5

N2 - The 5′ end of the flavivirus plus-sense RNA genome contains a type 1 cap (m7GpppAniG), followed by a conserved stem-loop structure. We report that nonstructural protein 5 (NS5) from four serocomplexes of flaviviruses specifically methylates the cap through recognition of the 5′ terminus of viral RNA. Distinct RNA elements are required for the methylations at guanine N-7 on the cap and ribose 2′-OH on the first transcribed nucleotide. In a West Nile virus (WNV) model, N-7 cap methylation requires specific nucleotides at the second and third positions and a 5′ stem-loop structure; in contrast, 2′-OH ribose methylation requires specific nucleotides at the first and second positions, with a minimum 5′ viral RNA of 20 nucleotides. The cap analogues GpppA and m7GpppA are not active substrates for WNV methytransferase. Footprinting experiments using Gppp- and m7Gppp-terminated RNAs suggest that the 5′ termini of RNA substrates interact with NS5 during the sequential methylation reactions. Cap methylations could be inhibited by an antisense oligomer targeting the first 20 nucleotides of WNV genome. The viral RNA-specific cap methylation suggests methyltransferase as a novel target for flavivirus drug discovery.

AB - The 5′ end of the flavivirus plus-sense RNA genome contains a type 1 cap (m7GpppAniG), followed by a conserved stem-loop structure. We report that nonstructural protein 5 (NS5) from four serocomplexes of flaviviruses specifically methylates the cap through recognition of the 5′ terminus of viral RNA. Distinct RNA elements are required for the methylations at guanine N-7 on the cap and ribose 2′-OH on the first transcribed nucleotide. In a West Nile virus (WNV) model, N-7 cap methylation requires specific nucleotides at the second and third positions and a 5′ stem-loop structure; in contrast, 2′-OH ribose methylation requires specific nucleotides at the first and second positions, with a minimum 5′ viral RNA of 20 nucleotides. The cap analogues GpppA and m7GpppA are not active substrates for WNV methytransferase. Footprinting experiments using Gppp- and m7Gppp-terminated RNAs suggest that the 5′ termini of RNA substrates interact with NS5 during the sequential methylation reactions. Cap methylations could be inhibited by an antisense oligomer targeting the first 20 nucleotides of WNV genome. The viral RNA-specific cap methylation suggests methyltransferase as a novel target for flavivirus drug discovery.

UR - http://www.scopus.com/inward/record.url?scp=34247564968&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247564968&partnerID=8YFLogxK

U2 - 10.1128/JVI.02455-06

DO - 10.1128/JVI.02455-06

M3 - Article

C2 - 17301144

AN - SCOPUS:34247564968

VL - 81

SP - 4412

EP - 4421

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 9

ER -