ArticleJournal of virology2006
Catalytic core of alphavirus nonstructural protein nsP4 possesses terminal adenylyltransferase activity.
Article in Journal of virology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.
- The life cycle of the alphaviruses: From an antiviral perspective.Antiviral research · 2023Pooled it
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- Alphavirus replicase and regulatory RNA elements in host interactions and viral vector engineering.Journal of virology · 2026Review
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- A fold switch regulates conformation of an alphavirus RNA-dependent RNA polymerase.Nucleic acids research · 2026Article
- Genomic characterization and evolutionary analysis of Chikungunya virus strains in Guangzhou, China, 2025.Virology journal · 2025Article
- Impact of pre-existing anti-replicase immunity on the efficacy of self-amplifying mRNA vaccines.Nature communications · 2025Article
- Trans-complementation of chikungunya virus replicase mutants reveals alphavirus replication complexity and supports antiviral tool development.PLoS pathogens · 2025Article
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- mRNA poly(A)-tail length is a battleground for coronavirus-host competition.bioRxiv : the preprint server for biology · 2025Article
- Minimal polymerase-containing precursor required for Chikungunya virus RNA synthesis.bioRxiv : the preprint server for biology · 2025Article
- A fold switch regulates conformation of an alphavirus virus RNA-dependent RNA polymerase.bioRxiv : the preprint server for biology · 2025Article
- The Interplay Between Therapeutic Self-Amplifying RNA and the Innate Immune System: Balancing Efficiency and Reactogenicity.International journal of molecular sciences · 2025Review
- Alphavirus nsP2: A Multifunctional Regulator of Viral Replication and Promising Target for Anti-Alphavirus Therapies.Reviews in medical virology · 2025Review
- Mechanistic insights into Sindbis virus infection: noncapped genomic RNAs enhance the translation of capped genomic RNAs to promote viral infectivity.Nucleic acids research · 2025Article
- Heterogeneous Ribonucleoprotein K Is a Host Regulatory Factor of Chikungunya Virus Replication in Astrocytes.Viruses · 2024Article
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- Distinct chikungunya virus polymerase palm subdomains contribute to viral protein accumulation and virion production.PLoS pathogens · 2024Article
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- Distinct chikungunya virus polymerase palm subdomains contribute to virus replication and virion assembly.bioRxiv : the preprint server for biology · 2024Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The RNA-dependent RNA polymerase nsP4 is an integral part of the alphavirus replication complex. To define the role of nsP4 in viral RNA replication and for a structure-function analysis, we expressed Sindbis virus nsP4 in Escherichia coli. The core catalytic domain of nsP4 (Delta97nsP4, a deletion of the N-terminal 97 amino acids), which consists of the predicted polymerase domain containing the GDD amino acid motif required for viral RNA synthesis, was stable against proteolytic degradation during expression. Therefore, the recombinant core domain and selected mutants were expressed and purified to homogeneity. We determined that Delta97nsP4 possesses terminal adenylyltransferase (TATase) activity, as it specifically catalyzed the addition of adenine to the 3' end of an acceptor RNA in the presence of divalent cations. Furthermore, Delta97nsP4 is unable to transfer other nucleotides (UTP, CTP, GTP, and dATP) to the acceptor RNA in the absence or presence of other nucleotides. Delta97nsP4 possessing a GDD-to-GAA mutation completely inactivates the enzymatic activity. However, a GDD-to-SNN mutation did not inactivate the enzyme but reduced its activity to approximately 45% of that of the wild type in the presence of Mg(2+). Investigation of the TATase of the GDD-to-SNN mutant revealed that it had TATase equivalent to that of the wild type in the presence of Mn(2+). Identification of Delta97nsP4 TATase activity suggests a novel function of the alphavirus RNA-dependent RNA polymerase in the maintenance and repair of the poly(A) tail, an element required for replication of the viral genome.
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Registered trials
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.