Coronavirus packaging signal

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Coronavirus packaging signal
Predicted secondary structure and sequence conservation of Corona_package
Other data
RNA typeCis-reg
PDB structuresPDBe

The Coronavirus packaging signal is a conserved cis-regulatory element found in Betacoronavirus (part of the Coronavirus subfamily of viruses). It has an important role in regulating the packaging of the viral genome into the capsid. As part of the viral life cycle, within the infected cell, the viral genome becomes associated with viral proteins and assembles into new infective progeny viruses. This process is called packaging and is vital for viral replication.

The packaging signal is found in the positive-sense single-stranded RNA genome. It interacts with the viral proteins (M and N)[1] and ensures the selective packaging of viral RNA into virions.[2]

This RNA element is conserved in Embecovirus (previously known as lineage A Betacoronavirus[3]), which includes mouse hepatitis virus (MHV), bovine coronavirus (BCoV), and human coronaviruses like HCoV-HKU1 and HCoV-OC43. Notably, this element is absent from the other viral lineages which have evolved separate packaging signals. For example, it is not found in SARS-CoV and SARS-CoV-2[1] (contrary to previous claims[4] that have been refuted[5]).

The packaging signal has a conserved RNA secondary structure featuring four AGC/GUAAU internal loop motifs.[6] Within the viral genome the packaging signal is located in the nonstructural protein 15 (nsp15) and encodes a polypeptide which is found on the surface of the nsp15 protein.[7] Deleting the packaging signal or introducing mutations that disrupt its secondary structure but not the encoded peptide lead to the loss of packaging specificity. At the same time, relocating the packaging signal to a different part of the genome did not have a negative effect on packaging.[8]

Other RNA families identified in the coronavirus include the coronavirus frameshifting stimulation element, the coronavirus 3′ stem-loop II-like motif (s2m), as well as the 5′- and 3′ UTR pseudoknot.

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  1. ^ a b Masters, PS (November 2019). "Coronavirus genomic RNA packaging". Virology. 537: 198–207. doi:10.1016/j.virol.2019.08.031. PMC 7112113. PMID 31505321.
  2. ^ Narayanan K, Makino S (2001). "Cooperation of an RNA packaging signal and a viral envelope protein in coronavirus RNA packaging". J. Virol. 75 (19): 9059–9067. doi:10.1128/JVI.75.19.9059-9067.2001. PMC 114474. PMID 11533169.
  3. ^ Wong, Antonio C. P.; Li, Xin; Lau, Susanna K. P.; Woo, Patrick C. Y. (February 2019). "Global Epidemiology of Bat Coronaviruses". Viruses. 11 (2): 174. doi:10.3390/v11020174. ISSN 1999-4915. PMC 6409556. PMID 30791586.
  4. ^ Qin, Lei; Xiong, Bin; Luo, Cheng; Guo, Zong-Ming; Hao, Pei; Su, Jiong; Nan, Peng; Feng, Ying; Shi, Yi-Xiang; Yu, Xiao-Jing; Luo, Xiao-Min (June 2003). "Identification of probable genomic packaging signal sequence from SARS-CoV genome by bioinformatics analysis". Acta Pharmacologica Sinica. 24 (6): 489–496. ISSN 1671-4083. PMID 12791173.
  5. ^ Kuo, Lili; Koetzner, Cheri A.; Hurst, Kelley R.; Masters, Paul S. (April 2014). "Recognition of the murine coronavirus genomic RNA packaging signal depends on the second RNA-binding domain of the nucleocapsid protein". Journal of Virology. 88 (8): 4451–4465. doi:10.1128/JVI.03866-13. ISSN 1098-5514. PMC 3993769. PMID 24501403.
  6. ^ Chen, Shih-Cheng; van den Born, Erwin; van den Worm, Sjoerd H. E.; Pleij, Cornelis W. A.; Snijder, Eric J.; Olsthoorn, René C. L. (June 2007). "New structure model for the packaging signal in the genome of group IIa coronaviruses". Journal of Virology. 81 (12): 6771–6774. doi:10.1128/JVI.02231-06. ISSN 0022-538X. PMC 1900089. PMID 17428856.
  7. ^ Xu, Xiaoling; Zhai, Yujia; Sun, Fei; Lou, Zhiyong; Su, Dan; Xu, Yuanyuan; Zhang, Rongguang; Joachimiak, Andrzej; Zhang, Xuejun C.; Bartlam, Mark; Rao, Zihe (August 2006). "New antiviral target revealed by the hexameric structure of mouse hepatitis virus nonstructural protein nsp15". Journal of Virology. 80 (16): 7909–7917. doi:10.1128/JVI.00525-06. ISSN 0022-538X. PMC 1563835. PMID 16873248.
  8. ^ Kuo, Lili; Masters, Paul S. (May 2013). "Functional Analysis of the Murine Coronavirus Genomic RNA Packaging Signal". Journal of Virology. 87 (9): 5182–5192. doi:10.1128/JVI.00100-13. ISSN 0022-538X. PMC 3624306. PMID 23449786.

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