Nidovirus ribonucleases: Structures and functions in viral replication

Ulferts, Rachel; Ziebuhr, John

doi:10.4161/rna.8.2.15196

Cited by 76 publications

(73 citation statements)

References 76 publications

(158 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The studies show that, in addition to common enzymes conserved in most +RNA viruses, such as RNAdependent RNA polymerase (RdRp) (te Velthuis et al, 2010), helicase/ NTPase (Seybert et al, 2000), proteases (Baker et al, 1989;Ziebuhr et al, 1995), 5 0 cap-specific methylases (Chen et al, 2009b;Decroly et al, 2008Decroly et al, , 2011, coronaviruses encode an extra set of proteins in their replicase genes. These additional (sometimes even unique) enzymatic functions include a 3 0 -5 0 exoribonuclease (Minskaia et al, 2006;Snijder et al, 2003) that is thought to be involved in mechanisms required for high-fidelity replication of nidovirus (including coronavirus) genomes of more than 20 kb (Eckerle et al, 2010;Minskaia et al, 2006;Smith et al, 2013Smith et al, , 2014) and a uridylate-specific endoribonuclease of currently unknown function that was found to be conserved in all vertebrate nidoviruses (Ivanov et al, 2004;Nga et al, 2011;Ulferts and Ziebuhr, 2011). In some cases, the replicase geneencoded enzymes could be linked to specific steps of viral RNA synthesis and/or RNA processing or were shown to interfere with cellular functions (reviewed in Fehr and Perlman, 2015;Masters and Perlman, 2013;Ziebuhr, 2008).…”

Section: Coronavirus Genome Replication and Transcriptionmentioning

confidence: 99%

Coronavirus cis-Acting RNA Elements

Madhugiri

Fricke

Marz

et al. 2016

Advances in Virus Research

102

111

View full text Add to dashboard Cite

Coronaviruses have exceptionally large RNA genomes of approximately 30 kilobases. Genome replication and transcription is mediated by a multisubunit protein complex comprised of more than a dozen virus-encoded proteins. The protein complex is thought to bind specific cis-acting RNA elements primarily located in the 5'- and 3'-terminal genome regions and upstream of the open reading frames located in the 3'-proximal one-third of the genome. Here, we review our current understanding of coronavirus cis-acting RNA elements, focusing on elements required for genome replication and packaging. Recent bioinformatic, biochemical, and genetic studies suggest a previously unknown level of conservation of cis-acting RNA structures among different coronavirus genera and, in some cases, even beyond genus boundaries. Also, there is increasing evidence to suggest that individual cis-acting elements may be part of higher-order RNA structures involving long-range and dynamic RNA-RNA interactions between RNA structural elements separated by thousands of nucleotides in the viral genome. We discuss the structural and functional features of these cis-acting RNA elements and their specific functions in coronavirus RNA synthesis.

show abstract

Section: Coronavirus Genome Replication and Transcriptionmentioning

confidence: 99%

Coronavirus cis-Acting RNA Elements

Madhugiri

Fricke

Marz

et al. 2016

Advances in Virus Research

102

111

View full text Add to dashboard Cite

show abstract

“…LSEI_0356 from Lactobacillus casei ATCC 334), which is present in several Type I-E CRISPR-Cas loci. In these fusion proteins, Cas2 appears to be inactivated as a result of substitution of the catalytic residues so that the ribonuclease activity is most likely supplied by the 3′-5′exonuclease-like domain [52]. …”

Section: Presentation Of the Hypothesismentioning

confidence: 99%

Live virus-free or die: coupling of antivirus immunity and programmed suicide or dormancy in prokaryotes

et al. 2012

View full text Add to dashboard Cite

BackgroundThe virus-host arms race is a major theater for evolutionary innovation. Archaea and bacteria have evolved diverse, elaborate antivirus defense systems that function on two general principles: i) immune systems that discriminate self DNA from nonself DNA and specifically destroy the foreign, in particular viral, genomes, whereas the host genome is protected, or ii) programmed cell suicide or dormancy induced by infection.Presentation of the hypothesisAlmost all genomic loci encoding immunity systems such as CRISPR-Cas, restriction-modification and DNA phosphorothioation also encompass suicide genes, in particular those encoding known and predicted toxin nucleases, which do not appear to be directly involved in immunity. In contrast, the immunity systems do not appear to encode antitoxins found in typical toxin-antitoxin systems. This raises the possibility that components of the immunity system themselves act as reversible inhibitors of the associated toxin proteins or domains as has been demonstrated for the Escherichia coli anticodon nuclease PrrC that interacts with the PrrI restriction-modification system. We hypothesize that coupling of diverse immunity and suicide/dormancy systems in prokaryotes evolved under selective pressure to provide robustness to the antivirus response. We further propose that the involvement of suicide/dormancy systems in the coupled antivirus response could take two distinct forms:1) induction of a dormancy-like state in the infected cell to ‘buy time’ for activation of adaptive immunity; 2) suicide or dormancy as the final recourse to prevent viral spread triggered by the failure of immunity.Testing the hypothesisThis hypothesis entails many experimentally testable predictions. Specifically, we predict that Cas2 protein present in all cas operons is a mRNA-cleaving nuclease (interferase) that might be activated at an early stage of virus infection to enable incorporation of virus-specific spacers into the CRISPR locus or to trigger cell suicide when the immune function of CRISPR-Cas systems fails. Similarly, toxin-like activity is predicted for components of numerous other defense loci.Implications of the hypothesisThe hypothesis implies that antivirus response in prokaryotes involves key decision-making steps at which the cell chooses the path to follow by sensing the course of virus infection.ReviewersThis article was reviewed by Arcady Mushegian, Etienne Joly and Nick Grishin. For complete reviews, go to the Reviewers’ reports section.

show abstract

“…All characterized family members display an RNA endonuclease activity producing 2'-3' cyclic phosphodiester and 5´-hydroxyl termini (Ulferts & Ziebuhr, 2011). All characterized family members display an RNA endonuclease activity producing 2'-3' cyclic phosphodiester and 5´-hydroxyl termini (Ulferts & Ziebuhr, 2011).…”

Section: Introductionmentioning

confidence: 99%

Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2

Kim

Jedrzejczak

Maltseva

et al. 2020

Preprint

104

187

View full text Add to dashboard Cite

ABSTRACTSevere Acute Respiratory Syndrome Coronavirus 2 is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS- and MERS-CoVs the detailed information about SARS-CoV-2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies and antivirals. We applied high-throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS-CoV-2 proteins and structures. Here we report the high-resolution crystal structure of endoribonuclease Nsp15/NendoU from SARS-CoV-2 – a virus causing current world-wide epidemics. We compare this structure with previously reported models of Nsp15 from SARS and MERS coronaviruses.

show abstract

Nidovirus ribonucleases: Structures and functions in viral replication

Cited by 76 publications

References 76 publications

Coronavirus cis-Acting RNA Elements

Coronavirus cis-Acting RNA Elements

Live virus-free or die: coupling of antivirus immunity and programmed suicide or dormancy in prokaryotes

Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2

Contact Info

Product

Resources

About