Accession	GSE226865
Status	2023/4/3
Title	Structure-first identification of RNA elements that regulate dengue virus genome architecture and replication
Organism	Dengue virus
Experiment type	Other
Summary	The genomes of RNA viruses encode the information required for replication in host cells both in their linear sequence and in complex higher-order structures. A subset of these RNA genome structures show clear sequence conservation, and have been extensively described for well-characterized viruses. However, the extent to which viral RNA genomes contain functional structural elements – unable to be detected by sequence alone – that nonetheless are critical to viral fitness is largely unknown. Here, we devise a structure-first experimental strategy and use it to identify 22 structure-similar motifs across the coding sequences of the RNA genomes for the four dengue virus (DENV) serotypes. At least ten of these motifs modulate viral fitness, revealing a significant unnoticed extent of RNA structure-mediated regulation within viral coding sequences. These viral RNA structures promote a compact global genome architecture, interact with proteins, and regulate the viral replication cycle. These motifs are also thus constrained at the levels of both RNA structure and protein sequence and are potential resistance-refractory targets for antivirals and live-attenuated vaccines. Structure-first identification of conserved RNA structure enables efficient discovery of pervasive RNA-mediated regulation in viral genomes and, likely, other cellular RNAs.
Samples	GSM ID Sample info Characteristics Description GSM7086062 DENV1 ex virion RNA 1M7 tissue:kidney; cell line:Vero; cell type:epithelial; treatment:10mM 1M7 reverse transcribed RNA;dengue virus 1;SHAPE-MaP GSM7086063 DENV1 ex virion RNA DMSO tissue:kidney; cell line:Vero; cell type:epithelial; treatment:DMSO reverse transcribed RNA;dengue virus 1;SHAPE-MaP GSM7086064 DENV2 ex virion RNA 1M7 tissue:kidney; cell line:Vero; cell type:epithelial; treatment:10mM 1M7 reverse transcribed RNA;dengue virus 2;SHAPE-MaP GSM7086065 DENV2 ex virion RNA DMSO tissue:kidney; cell line:Vero; cell type:epithelial; treatment:DMSO reverse transcribed RNA;dengue virus 2;SHAPE-MaP GSM7086066 DENV3 ex virion RNA 1M7 tissue:kidney; cell line:Vero; cell type:epithelial; treatment:10mM 1M7 reverse transcribed RNA;dengue virus 3;SHAPE-MaP GSM7086067 DENV3 ex virion RNA DMSO tissue:kidney; cell line:Vero; cell type:epithelial; treatment:DMSO reverse transcribed RNA;dengue virus 3;SHAPE-MaP GSM7086068 DENV4 ex virion RNA 1M7 tissue:kidney; cell line:Vero; cell type:epithelial; treatment:10mM 1M7 reverse transcribed RNA;dengue virus 4;SHAPE-MaP GSM7086069 DENV4 ex virion RNA DMSO tissue:kidney; cell line:Vero; cell type:epithelial; treatment:DMSO reverse transcribed RNA;dengue virus 4;SHAPE-MaP GSM7086070 DENV2 8500 WT in cell RNA SDA tissue:kidney; cell line:BHK-21; cell type:fibroblast; treatment:3J-UV and 10mM SDA reverse transcribed RNA;dengue virus 2;RNP-MaP GSM7086071 DENV2 8500 WT in cell RNA DMSO tissue:kidney; cell line:BHK-21; cell type:fibroblast; treatment:DMSO reverse transcribed RNA;dengue virus 2;RNP-MaP GSM7086072 DENV2 8500 Lock Mutant in cell RNA SDA tissue:kidney; cell line:BHK-21; cell type:fibroblast; treatment:3J-UV and 10mM SDA reverse transcribed RNA;dengue virus 2;RNP-MaP GSM7086073 DENV2 8500 Lock Mutant in cell RNA DMSO tissue:kidney; cell line:BHK-21; cell type:fibroblast; treatment:DMSO reverse transcribed RNA;dengue virus 2;RNP-MaP
Platform	GPL33221  GPL33222  GPL33223  GPL33224  : Illumina MiSeq (dengue virus type I);Illumina MiSeq (Dengue virus type 2);Illumina MiSeq (Dengue virus type 3);Illumina MiSeq (Dengue virus type 4)
Literature	37011200