Article Synopsis
- Coronaviruses are unique RNA viruses with large genomes (about 30 kb) and low mutation rates, which contribute to their stability.
- nsp14, a crucial enzyme in Coronaviruses, has two functions: it methylates RNA and proofreads by removing mismatched nucleotides, ensuring genetic stability.
- The study reveals how nsp14 interacts with nsp12 to manage RNA synthesis and proofreading, explaining the limited efficacy of the antiviral drug ribavirin, and presents a detailed structure of nsp14 that showcases its distinct features compared to other RNA viruses.
Video Abstracts
Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Coronaviruses (CoVs) stand out among RNA viruses because of their unusually large genomes (∼30 kb) associated with low mutation rates. CoVs code for nsp14, a bifunctional enzyme carrying RNA cap guanine N7-methyltransferase (MTase) and 3'-5' exoribonuclease (ExoN) activities. ExoN excises nucleotide mismatches at the RNA 3'-end in vitro, and its inactivation in vivo jeopardizes viral genetic stability. Here, we demonstrate for severe acute respiratory syndrome (SARS)-CoV an RNA synthesis and proofreading pathway through association of nsp14 with the low-fidelity nsp12 viral RNA polymerase. Through this pathway, the antiviral compound ribavirin 5'-monophosphate is significantly incorporated but also readily excised from RNA, which may explain its limited efficacy in vivo. The crystal structure at 3.38 Å resolution of SARS-CoV nsp14 in complex with its cofactor nsp10 adds to the uniqueness of CoVs among RNA viruses: The MTase domain presents a new fold that differs sharply from the canonical Rossmann fold.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777078 | PMC |
| http://dx.doi.org/10.1073/pnas.1718806115 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Single-cell atlas in the living fossil Yangtze sturgeon provides insight into the evolution of fish.
Genome Biol
September 2025
Fisheries Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu, 611730, China.
Background: Fish are the largest group of vertebrates. Studying the characteristics, functions, and interactions of different fish cells is important for understanding their roles in disease and evolution. However, most single cell RNA-seq studies in fish are restricted to a few specific organs, leaving a comprehensive cell landscape that aims to characterize the heterogeneity and connections among body-wide organs largely unexplored.
View Article and Find Full Text PDFUnraveling biomolecular interactions: a comprehensive review of the electromobility shift assay.
Photochem Photobiol Sci
September 2025
Department of Genetics and Plant Breeding, C. P. College of Agriculture, S. D. Agricultural University, Sardarkrushinagar, 385506, India.
The electromobility shift assay (EMSA) is a popular and productive molecular biology tool for studying protein-nucleic acid interactions. EMSA is a technique applied to the revelation of the binding dynamics of proteins, like transcription factors, to DNA or RNA. There are ample essential phases in the technique.
View Article and Find Full Text PDFThe impact of miRNAs on epithelial-mesenchymal transition in lung cancer and the latest advances in their use as diagnostic markers.
J Cancer Res Clin Oncol
September 2025
Inner Mongolia Medical University Affiliated Hospital, Hohhot, 010030, Inner Mongolia, China.
Purpose: Lung cancer is currently the most common malignant tumor worldwide and one of the leading causes of cancer-related deaths, posing a serious threat to human health. MicroRNAs (miRNAs) are a class of endogenous non-coding small RNA molecules that regulate gene expression and are involved in various biological processes associated with lung cancer. Understanding the mechanisms of lung carcinogenesis and detecting disease biomarkers may enable early diagnosis of lung cancer.
View Article and Find Full Text PDFExploring Differentially Expressed Genes and Understanding the Underlying Mechanisms in Glioblastoma.
Biochem Genet
September 2025
Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University Cerrahpasa, Kocamustafapasa, 34098, Istanbul, Turkey.
Glioblastoma is the most aggressive and malignant tumor of the central nervous system. Current treatment options, including surgical excision, radiotherapy, and chemotherapy, have Limited efficacy, with a median survival rate of approximately 15 months. To develop novel therapeutics, it is crucial to understand the underlying molecular mechanisms driving glioblastoma.
View Article and Find Full Text PDFAssessment of genomic prediction capabilities of transcriptome data in a barley multi-parent RIL population.
Theor Appl Genet
September 2025
Institute for Breeding Research on Agricultural Crops, Julius Kühn Institute (JKI) - Federal Research Centre for Cultivated Plants, Sanitz, 18190, Germany.
Low-cost and high-throughput RNA sequencing data for barley RILs achieved GP performance comparable to or better than traditional SNP array datasets when combined with parental whole-genome sequencing SNP data. The field of genomic selection (GS) is advancing rapidly on many fronts including the utilization of multi-omics datasets with the goal of increasing prediction ability and becoming an integral part of an increasing number of breeding programs ensuring future food security. In this study, we used RNA sequencing (RNA-Seq) data to perform genomic prediction (GP) on three related barley RIL populations.
View Article and Find Full Text PDF