NS5 acts as a cap 2'-O-methyltransferase to methylate 5’ m7GpppA of DENV genomic +ssRNA

Stable Identifier
R-HSA-9923097
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Dengue virus type 2
Compartment
cytosol
ReviewStatus
5/5
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NS5 acts as a cap 2'-O-methyltransferase to methylate 5’ m7GpppA of DENV genomic +ssRNA
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NS5 subunit of the DENV Replication Complex (RC) catalyzes 2’O-methylation of viral genomic m7GpppA-capped +ssRNA (cap0), using S-adenosyl-L-methionine (SAM) as a methyl donor, producing a cap1 structure labeled m7G(5')pppAm (Ray et al., 2006; Egloff et al., 2002). Part of the free +ssRNA supports translation into polyprotein in the early stage of cell infection, while in later stages newly synthesized genomic +ssRNA serves as a template for further translation or packaging into progeny virions (Fajardo et al., 2020). 2'-O-methylation of DENV-1 RNA appears to be a factor in evasion of the host's early innate immune response (Chang et al., 2016).
Literature References
PubMed ID Title Journal Year
32313955 The flavivirus polymerase NS5 regulates translation of viral genomic RNA

Fajardo, T, Sanford, TJ, Mears, HV, Jasper, A, Storrie, S, Mansur, DS, Sweeney, TR

Nucleic Acids Res 2020
12032088 An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization

Egloff, MP, Benarroch, D, Selisko, B, Romette, JL, Canard, B

EMBO J 2002
27716465 Evasion of early innate immune response by 2'-O-methylation of dengue genomic RNA

Chang, DC, Hoang, LT, Mohamed Naim, AN, Dong, H, Schreiber, MJ, Hibberd, ML, Tan, MJA, Shi, PY

Virology 2016
16912287 West Nile virus 5'-cap structure is formed by sequential guanine N-7 and ribose 2'-O methylations by nonstructural protein 5

Ray, D, Shah, A, Tilgner, M, Guo, Y, Zhao, Y, Dong, H, Deas, TS, Zhou, Y, Li, H, Shi, PY

J. Virol. 2006
Participants
Input
Output
Participates
as an event of
Catalyst Activity

methyltransferase cap1 activity of DENV m7G(5')ppp-+ssRNA:RC [endoplasmic reticulum membrane]

Physical Entity
DENV m7G(5')ppp-+ssRNA:RC [endoplasmic reticulum membrane] (Dengue virus type 2)
Activity
methyltransferase cap1 activity (GO:0004483)
Disease
Name Identifier Synonyms
dengue disease DOID:12205 breakbone fever, Dengue Fever, classic dengue
Cross References
RHEA
Mondo
Authored
Stephan, R  (2024-10-07)
Reviewed
Mansur, DS  (2025-09-18)
Roque Ascenção, F  (2025-10-29)
Roque Ascenção, F  (2026-03-03)
Created
Stephan, R  (2024-09-30)
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