Characterization of an efficient coronavirus ribosomal frameshifting signal: Requirement for an RNA pseudoknot

Brierley, Ian; Digard, Paul; Inglis, Stephen

doi:10.1016/0092-8674(89)90124-4

Cited by 651 publications

(707 citation statements)

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“…For most of them, the mechanisms used to express the downstream ORFs remain to be determined. On the basis of the available data for other coronaviruses (Brierley et al, 1989;Eleouet et al, 1995;Herold et al, 1993;Kocherhans et al, 2001), it seemed likely that ORF1b expression from the genomic RNA would involve 21 ribosomal frameshifting, a process that essentially depends on two elements, known as the 'slippery' sequence, i.e. the site where the ribosomes shift into the 21 reading frame, and a complex RNA pseudoknot structure (Brierley et al, 1989.…”

Section: Translationmentioning

confidence: 99%

“…On the basis of the available data for other coronaviruses (Brierley et al, 1989;Eleouet et al, 1995;Herold et al, 1993;Kocherhans et al, 2001), it seemed likely that ORF1b expression from the genomic RNA would involve 21 ribosomal frameshifting, a process that essentially depends on two elements, known as the 'slippery' sequence, i.e. the site where the ribosomes shift into the 21 reading frame, and a complex RNA pseudoknot structure (Brierley et al, 1989. Analysis of the SARS-CoV sequence flanking the ORF1a termination codon revealed a putative SARSCoV frameshifting element comprised of a putative 'slippery' sequence ( 13392 UUUAAAC 13398 ) and, further downstream, stretches of complementary sequences that can be modelled to form a typical pseudoknot structure (Fig.…”

Section: Translationmentioning

confidence: 99%

“…1). Expression of the ORF1b-encoded region of pp1ab is predicted to involve ribosomal frameshifting into the 21 frame just upstream of the ORF1a translation termination codon (Brierley et al, 1989). The pp1a and pp1ab polyproteins are processed by viral proteinases to yield the functional components of the membrane-bound replicase complex (Ziebuhr et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms and enzymes involved in SARS coronavirus genome expression

Thiel

Иванов

Putics

et al. 2003

Journal of General Virology

804

960

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A novel coronavirus is the causative agent of the current epidemic of severe acute respiratory syndrome (SARS). Coronaviruses are exceptionally large RNA viruses and employ complex regulatory mechanisms to express their genomes. Here, we determined the sequence of SARS coronavirus (SARS-CoV), isolate Frankfurt 1, and characterized key RNA elements and protein functions involved in viral genome expression. Important regulatory mechanisms, such as the (discontinuous) synthesis of eight subgenomic mRNAs, ribosomal frameshifting and posttranslational proteolytic processing, were addressed. Activities of three SARS coronavirus enzymes, the helicase and two cysteine proteinases, which are known to be critically involved in replication, transcription and/or post-translational polyprotein processing, were characterized. The availability of recombinant forms of key replicative enzymes of SARS coronavirus should pave the way for high-throughput screening approaches to identify candidate inhibitors in compound libraries. INTRODUCTIONSevere acute respiratory syndrome (SARS) is a lifethreatening form of pneumonia (Peiris et al., 2003a). In the course of a few months in 2003, an epidemic emerged that has spread from its likely origin in Guangdong Province, China, to 32 countries. By 11 June 2003 more than 8400 cases and 789 deaths had been recorded by the World Health Organization. The rapid transmission by aerosols (and probably also the faecal-oral route) and the high mortality rate make SARS a global threat for which no efficacious therapy is available. There is now clear evidence that SARS is caused by a previously unknown coronavirus, provisionally termed SARS coronavirus (SARS-CoV) (Peiris et al., 2003b;Drosten et al., 2003;Ksiazek et al., 2003;Fouchier et al., 2003). Genome sequences of SARS-CoV isolates obtained from a number of index patients have been published recently and provide important information on the organization, phylogeny and variability of the 29?7 kb positive-strand RNA genome of SARS-CoV (Rota et al., 2003;Marra et al., 2003;Ruan et al., 2003). By analogy with other coronaviruses (Lai & Holmes, 2001;Gorbalenya, 2001), SARS-CoV gene expression is expected to involve complex transcriptional, translational and post-translational regulatory mechanisms, whose molecular details remain to be determined. SARS-CoV genome expression starts with the translation of two large replicative polyproteins, pp1a (486 kDa) and pp1ab (790 kDa), which are encoded by the viral replicase gene (21 221 nt) that comprises ORFs 1a and 1b (Fig. 1). Expression of the ORF1b-encoded region of pp1ab is predicted to involve ribosomal frameshifting into the 21 frame just upstream of the ORF1a translation termination codon (Brierley et al., 1989). The pp1a and pp1ab polyproteins are processed by viral proteinases to yield the functional components of the membrane-bound replicase complex (Ziebuhr et al., 2000). In contrast to most other coronaviruses, which use three proteinase activities for replicase polyprotein processing (Ziebuhr et ...

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Section: Translationmentioning

confidence: 99%

Section: Translationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mechanisms and enzymes involved in SARS coronavirus genome expression

Thiel

Иванов

Putics

et al. 2003

Journal of General Virology

804

960

View full text Add to dashboard Cite

show abstract

“…The pKT0/NS1 expression vector carries the packaging signals for the filamentous bacteriophage fl (Dotto et al, 1981) enabling the rescue of ssDNA following superinfection of bacterial cells (bearing the plasmid) with phage R408 (Russel et al, 1986). Oligonucleotide-directed mutagenesis (Kunkel, 1985) was carried out as described by Brierley et al (1989).…”

Section: Methodsmentioning

confidence: 99%

“…Data have been reported demonstrating ribosomal frameshifting between ORFs la and lb (Brierley et al, 1987(Brierley et al, , 1989 which allows readthrough of the la stop codon and therefore expression of lb (which does not have its own subgenomic mRNA) as a fusion product la/lb. Thus, translation of gene 1 would result potentially in a stopped product (from ORF la) of 441 kDa and a read-through product (from la/lb) of 741 kDa.…”

Section: Introductionmentioning

confidence: 99%

A region of the coronavirus infectious bronchitis virus 1a polyprotein encoding the 3C-like protease domain is subject to rapid turnover when expressed in rabbit reticulocyte lysate

Tibbles¹,

Brierley²,

Cavanagh³

et al. 1995

Journal of General Virology

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In order to investigate the mechanisms involved in the processing of infectious bronchitis virus polyproteins, several candidate regions of the genome have been cloned and expressed in vitro. During these studies it was observed that the translation product encoded by one of these clones (pKT205) was poorly expressed. Biochemical and genetic analyses revealed that the basis for the poor expression was a post-translational event involving ubiquitination of the protein and degradation by an ATP-dependent system operating in the reticulocyte lysate used for the in vitro expression. Two independently acting regions which conferred instability were identified, one of which mapped to the predicted 3C protease domain, contained within the 5' end of the clone, while the other, more C-terminal region, was effective in conferring instability upon a heterologous protein to which it had been transferred. These regions may influence the stability of the authentic viral protein(s) in vivo and hence allow for the control of their expression and/or function at the level of proteolysis by cellular protease(s).

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RNA‐virus proteases counteracting host innate immunity

Lei

Hilgenfeld

2017

FEBS Letters

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Virus invasion triggers host immune responses, in particular, innate immune responses. Pathogen‐associated molecular patterns of viruses (such as dsRNA, ssRNA, or viral proteins) released during virus replication are detected by the corresponding pattern‐recognition receptors of the host, and innate immune responses are induced. Through production of type‐I and type‐III interferons as well as various other cytokines, the host innate immune system forms the frontline to protect host cells and inhibit virus infection. Not surprisingly, viruses have evolved diverse strategies to counter this antiviral system. In this review, we discuss the multiple strategies used by proteases of positive‐sense single‐stranded RNA viruses of the families Picornaviridae, Coronaviridae, and Flaviviridae, when counteracting host innate immune responses.

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Characterization of an efficient coronavirus ribosomal frameshifting signal: Requirement for an RNA pseudoknot

Cited by 651 publications

References 38 publications

Mechanisms and enzymes involved in SARS coronavirus genome expression

Mechanisms and enzymes involved in SARS coronavirus genome expression

A region of the coronavirus infectious bronchitis virus 1a polyprotein encoding the 3C-like protease domain is subject to rapid turnover when expressed in rabbit reticulocyte lysate

RNA‐virus proteases counteracting host innate immunity

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