ArticleJournal of virology2014
Reselection of a genomic upstream open reading frame in mouse hepatitis coronavirus 5'-untranslated-region mutants.
Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
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- Identification and comparison of RNA structures in 5'- and 3'-terminal genomic regions across four coronavirus genera by SHAPE analysis.Virology journal · 2026Article
- Flexibility and modulation of translation initiation in enterovirus genomes.PLoS pathogens · 2026Article
- The transcriptional and translational landscape of HCoV-OC43 infection.PLoS pathogens · 2025Article
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- Tiny but mighty: Diverse functions of uORFs that regulate gene expression.Computational and structural biotechnology journal · 2024Review
- Preferential cleavage of the coronavirus defective viral genome by cellular endoribonuclease with characteristics of RNase L.Virology journal · 2024Article
- Host-like RNA Elements Regulate Virus Translation.Viruses · 2024Review
- Bioinformatics Insights on Viral Gene Expression Transactivation: From HIV-1 to SARS-CoV-2.International journal of molecular sciences · 2024Article
- SARS-CoV-2 Nsp1 cooperates with initiation factors EIF1 and 1A to selectively enhance translation of viral RNA.PLoS pathogens · 2024Article
- Coronavirus takeover of host cell translation and intracellular antiviral response: a molecular perspective.The EMBO journal · 2024Review
- High-resolution structure of stem-loop 4 from the 5'-UTR of SARS-CoV-2 solved by solution state NMR.Nucleic acids research · 2023Article
- Unveiling the biology of defective viral genomes in vitro and in vivo: implications for gene expression and pathogenesis of coronavirus.Virology journal · 2023Article
- Lessons Learned and Yet-to-Be Learned on the Importance of RNA Structure in SARS-CoV-2 Replication.Microbiology and molecular biology reviews : MMBR · 2022Review
- Computational Pipeline for Reference-Free Comparative Analysis of RNA 3D Structures Applied to SARS-CoV-2 UTR Models.International journal of molecular sciences · 2022Article
- Article
- The role of upstream open reading frames in translation regulation in the apicomplexan parasitesParasitology · 2021Review
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- Structure and regulation of coronavirus genomes: state-of-the-art and novel insights from SARS-CoV-2 studies.Biochemical Society transactions · 2021Review
- Analysis of Emerging Variants in Structured Regions of the SARS-CoV-2 Genome.Evolutionary bioinformatics online · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
An AUG-initiated upstream open reading frame (uORF) encoding a potential polypeptide of 3 to 13 amino acids (aa) is found within the 5' untranslated region (UTR) of >75% of coronavirus genomes based on 38 reference strains. Potential CUG-initiated uORFs are also found in many strains. The AUG-initiated uORF is presumably translated following genomic 5'-end cap-dependent ribosomal scanning, but its function is unknown. Here, in a reverse-genetics study with mouse hepatitis coronavirus, the following were observed. (i) When the uORF AUG-initiating codon was replaced with a UAG stop codon along with a U112A mutation to maintain a uORF-harboring stem-loop 4 structure, an unimpaired virus with wild-type (WT) growth kinetics was recovered. However, reversion was found at all mutated sites within five virus passages. (ii) When the uORF was fused with genomic (main) ORF1 by converting three in-frame stop codons to nonstop codons, a uORF-ORF1 fusion protein was made, and virus replicated at WT levels. However, a frameshifting G insertion at virus passage 7 established a slightly 5'-extended original uORF. (iii) When uAUG-eliminating deletions of 20, 30, or 51 nucleotides (nt) were made within stem-loop 4, viable but debilitated virus was recovered. However, a C80U mutation in the first mutant and an A77G mutation in the second appeared by passage 10, which generated alternate uORFs that correlated with restored WT growth kinetics. In vitro, the uORF-disrupting nondeletion mutants showed enhanced translation of the downstream ORF1 compared with the WT. These results together suggest that the uORF represses ORF1 translation yet plays a beneficial but nonessential role in coronavirus replication in cell culture.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.