Novel conserved RNA structural motifs regulate genome cyclization of yellow fever virus
- 1Sun Yat-sen University
Abstract
The long-range RNA-RNA interaction between the termini of a flavivirus genome is controlled by multiple local RNA secondary and tertiary structures. However, a complete picture of this essential genome cyclization process is still elusive. Herein, by using selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE), SHAPE and mutational profiling, in vitro RNA binding assays, and reverse genetics approaches, we demonstrated that the hairpin 2 in the capsid-coding region (cHP2) is required for efficient replication of yellow fever virus and functionally interacts with the 3'-small hairpin (sHP) during genome cyclization. Interestingly, through a combination of multidimensional chemical probing and functional characterization assays, it was discovered that the sHP forms previously unknown tertiary interactions with an immediately upstream GACG region embedded within the 3'-cyclization sequence. This crucial tertiary RNA motif accounts for a potential negative regulatory mechanism of genome cyclization and is universally conserved among the mosquito-borne-related flaviviruses, which constitute a major phylogenetic branch within the subgenus Euflavivirus, genus Orthoflavivirus. Our study highlights the intricacy of RNA-based regulation in flaviviruses.
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BibTeX
@misc{luo2026novel,
title = {{Novel conserved RNA structural motifs regulate genome cyclization of yellow fever virus}},
author = {Y.-G. Luo and J.-Y. Zhang and D. Li and Y.-T. Xie and H.-T. Lu and X.-M. Feng and Y.-Z. Ding and H.-Y. Zhou and C.-F. Qin and Z.-Y. Liu},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.23.753880},
url = {https://www.biorxiv.org/content/10.64898/2026.09.23.753880v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Novel conserved RNA structural motifs regulate genome cyclization of yellow fever virus
AU - Y.-G. Luo
AU - J.-Y. Zhang
AU - D. Li
AU - Y.-T. Xie
AU - H.-T. Lu
AU - X.-M. Feng
AU - Y.-Z. Ding
AU - H.-Y. Zhou
AU - C.-F. Qin
AU - Z.-Y. Liu
PY - 2026
DA - 2026/09/23
PB - bioRxiv
DO - 10.64898/2026.09.23.753880
UR - https://www.biorxiv.org/content/10.64898/2026.09.23.753880v1
AB - The long-range RNA-RNA interaction between the termini of a flavivirus genome is controlled by multiple local RNA secondary and tertiary structures. However, a complete picture of this essential genome cyclization process is still elusive. Herein, by using selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE), SHAPE and mutational profiling, in vitro RNA binding assays, and reverse genetics approaches, we demonstrated that the hairpin 2 in the capsid-coding region (cHP2) is required for efficient replication of yellow fever virus and functionally interacts with the 3'-small hairpin (sHP) during genome cyclization. Interestingly, through a combination of multidimensional chemical probing and functional characterization assays, it was discovered that the sHP forms previously unknown tertiary interactions with an immediately upstream GACG region embedded within the 3'-cyclization sequence. This crucial tertiary RNA motif accounts for a potential negative regulatory mechanism of genome cyclization and is universally conserved among the mosquito-borne-related flaviviruses, which constitute a major phylogenetic branch within the subgenus Euflavivirus, genus Orthoflavivirus. Our study highlights the intricacy of RNA-based regulation in flaviviruses.
ER -