Nucleocapsid phosphorylation and RNA helicase DDX1 recruitment enables coronavirus transition from discontinuous to continuous transcription
- PMID: 25299332
- PMCID: PMC7104987
- DOI: 10.1016/j.chom.2014.09.009
Nucleocapsid phosphorylation and RNA helicase DDX1 recruitment enables coronavirus transition from discontinuous to continuous transcription
Abstract
Coronaviruses contain a positive-sense single-stranded genomic (g) RNA, which encodes nonstructural proteins. Several subgenomic mRNAs (sgmRNAs) encoding structural proteins are generated by template switching from the body transcription regulatory sequence (TRS) to the leader TRS. The process preferentially generates shorter sgmRNA. Appropriate readthrough of body TRSs is required to produce longer sgmRNAs and full-length gRNA. We find that phosphorylation of the viral nucleocapsid (N) by host glycogen synthase kinase-3 (GSK-3) is required for template switching. GSK-3 inhibition selectively reduces the generation of gRNA and longer sgmRNAs, but not shorter sgmRNAs. N phosphorylation allows recruitment of the RNA helicase DDX1 to the phosphorylated-N-containing complex, which facilitates template readthrough and enables longer sgmRNA synthesis. DDX1 knockdown or loss of helicase activity markedly reduces the levels of longer sgmRNAs. Thus, coronaviruses employ a unique strategy for the transition from discontinuous to continuous transcription to ensure balanced sgmRNAs and full-length gRNA synthesis.
Copyright © 2014 Elsevier Inc. All rights reserved.
Figures
Similar articles
-
Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Protein Interacts with Nsp9 and Cellular DHX9 To Regulate Viral RNA Synthesis.J Virol. 2016 May 12;90(11):5384-5398. doi: 10.1128/JVI.03216-15. Print 2016 Jun 1. J Virol. 2016. PMID: 27009951 Free PMC article.
-
Continuous and Discontinuous RNA Synthesis in Coronaviruses.Annu Rev Virol. 2015 Nov;2(1):265-88. doi: 10.1146/annurev-virology-100114-055218. Annu Rev Virol. 2015. PMID: 26958916 Free PMC article. Review.
-
Gene N proximal and distal RNA motifs regulate coronavirus nucleocapsid mRNA transcription.J Virol. 2011 Sep;85(17):8968-80. doi: 10.1128/JVI.00869-11. Epub 2011 Jun 29. J Virol. 2011. PMID: 21715479 Free PMC article.
-
Subgenomic messenger RNA amplification in coronaviruses.Proc Natl Acad Sci U S A. 2010 Jul 6;107(27):12257-62. doi: 10.1073/pnas.1000378107. Epub 2010 Jun 18. Proc Natl Acad Sci U S A. 2010. PMID: 20562343 Free PMC article.
-
A new model for coronavirus transcription.Adv Exp Med Biol. 1998;440:215-9. doi: 10.1007/978-1-4615-5331-1_26. Adv Exp Med Biol. 1998. PMID: 9782283 Review.
Cited by
-
Variant mutation in SARS-CoV-2 nucleocapsid enhances viral infection via altered genomic encapsidation.bioRxiv [Preprint]. 2024 Mar 11:2024.03.08.584120. doi: 10.1101/2024.03.08.584120. bioRxiv. 2024. PMID: 38559000 Free PMC article. Preprint.
-
Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication and pathogenicity.Cell Rep. 2024 Mar 26;43(3):113965. doi: 10.1016/j.celrep.2024.113965. Epub 2024 Mar 15. Cell Rep. 2024. PMID: 38492217 Free PMC article.
-
Classification, replication, and transcription of Nidovirales.Front Microbiol. 2024 Jan 24;14:1291761. doi: 10.3389/fmicb.2023.1291761. eCollection 2023. Front Microbiol. 2024. PMID: 38328580 Free PMC article. Review.
-
The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L interactions.EMBO Rep. 2024 Feb;25(2):902-926. doi: 10.1038/s44319-023-00043-z. Epub 2024 Jan 2. EMBO Rep. 2024. PMID: 38177924 Free PMC article.
-
Sex differences in the cardiac stress response following SARS-CoV-2 infection of ferrets.Am J Physiol Heart Circ Physiol. 2023 Nov 1;325(5):H1153-H1167. doi: 10.1152/ajpheart.00101.2023. Epub 2023 Sep 22. Am J Physiol Heart Circ Physiol. 2023. PMID: 37737732 Free PMC article.
References
-
- Calvo E., Escors D., López J.A., González J.M., Alvarez A., Arza E., Enjuanes L. Phosphorylation and subcellular localization of transmissible gastroenteritis virus nucleocapsid protein in infected cells. J. Gen. Virol. 2005;86:2255–2267. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous