A unique cap(m7GpppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription
TL;DR: It is shown that virions and purified viral cores contain a unique endonuclease that cleaves RNAs containing a 5' methylated cap structure preferentially at purine residues 10 to 14 nucleotides from the cap, generating fragments with 3'-terminal hydroxyl groups.
About: This article is published in Cell.The article was published on 1981-03-01. It has received 716 citations till now. The article focuses on the topics: Cap snatching & RNA.
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Texas A&M University1, Agricultural Research Service2, Hebrew University of Jerusalem3, Seoul Women's University4, University of Rennes5, University of Basel6, Norwich Research Park7, University of Bordeaux8, University of Wisconsin-Madison9, North Carolina State University10, University of Bristol11
TL;DR: A short review on each virus of the Top 10 list and its importance is presented, with the intent of initiating discussion and debate amongst the plant virology community, as well as laying down a benchmark, as it will be interesting to see in future years how perceptions change and which viruses enter and leave the Top10.
Abstract: Many scientists, if not all, feel that their particular plant virus should appear in any list of the most important plant viruses. However, to our knowledge, no such list exists. The aim of this review was to survey all plant virologists with an association with Molecular Plant Pathology and ask them to nominate which plant viruses they would place in a 'Top 10' based on scientific/economic importance. The survey generated more than 250 votes from the international community, and allowed the generation of a Top 10 plant virus list for Molecular Plant Pathology. The Top 10 list includes, in rank order, (1) Tobacco mosaic virus, (2) Tomato spotted wilt virus, (3) Tomato yellow leaf curl virus, (4) Cucumber mosaic virus, (5) Potato virus Y, (6) Cauliflower mosaic virus, (7) African cassava mosaic virus, (8) Plum pox virus, (9) Brome mosaic virus and (10) Potato virus X, with honourable mentions for viruses just missing out on the Top 10, including Citrus tristeza virus, Barley yellow dwarf virus, Potato leafroll virus and Tomato bushy stunt virus. This review article presents a short review on each virus of the Top 10 list and its importance, with the intent of initiating discussion and debate amongst the plant virology community, as well as laying down a benchmark, as it will be interesting to see in future years how perceptions change and which viruses enter and leave the Top 10.
842 citations
Cites background from "A unique cap(m7GpppXm)-dependent in..."
...…to mention: (i) virions contain the viral RNA-dependent RNA polymerase which uses host cell mRNAs to prime viral transcription via cap-snatching (Plotch et al., 1981); and (ii) thrips can only transmit TSWV if acquired as larvae, although both larvae and adults are able to transmit (reviewed in…...
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TL;DR: In this paper, the amino-terminal 209 residues of the PA subunit contain the active site of the endonuclease active site, which is shown to be strongly activated by manganese ions, matching observations reported for the intact trimeric polymerase.
Abstract: The influenza virus polymerase, a heterotrimer composed of three subunits, PA, PB1 and PB2, is responsible for replication and transcription of the eight separate segments of the viral RNA genome in the nuclei of infected cells. The polymerase synthesizes viral messenger RNAs using short capped primers derived from cellular transcripts by a unique 'cap-snatching' mechanism. The PB2 subunit binds the 5' cap of host pre-mRNAs, which are subsequently cleaved after 10-13 nucleotides by the viral endonuclease, hitherto thought to reside in the PB2 (ref. 5) or PB1 (ref. 2) subunits. Here we describe biochemical and structural studies showing that the amino-terminal 209 residues of the PA subunit contain the endonuclease active site. We show that this domain has intrinsic RNA and DNA endonuclease activity that is strongly activated by manganese ions, matching observations reported for the endonuclease activity of the intact trimeric polymerase. Furthermore, this activity is inhibited by 2,4-dioxo-4-phenylbutanoic acid, a known inhibitor of the influenza endonuclease. The crystal structure of the domain reveals a structural core closely resembling resolvases and type II restriction endonucleases. The active site comprises a histidine and a cluster of three acidic residues, conserved in all influenza viruses, which bind two manganese ions in a configuration similar to other two-metal-dependent endonucleases. Two active site residues have previously been shown to specifically eliminate the polymerase endonuclease activity when mutated. These results will facilitate the optimisation of endonuclease inhibitors as potential new anti-influenza drugs.
715 citations
TL;DR: Accumulating evidence on how viral infection and PRR signalling pathways intersect is providing further insights into the function of the pathways involved, their constituent proteins and ways in which they could be manipulated therapeutically.
Abstract: The expression of pattern-recognition receptors (PRRs) by immune and tissue cells provides the host with the ability to detect and respond to infection by viruses and other microorganisms. Significant progress has been made from studying this area, including the identification of PRRs, such as Toll-like receptors and RIG-I-like receptors, and the description of the molecular basis of their signalling pathways, which lead to the production of interferons and other cytokines. In parallel, common mechanisms used by viruses to evade PRR-mediated responses or to actively subvert these pathways for their own benefit are emerging. Accumulating evidence on how viral infection and PRR signalling pathways intersect is providing further insights into the function of the pathways involved, their constituent proteins and ways in which they could be manipulated therapeutically.
655 citations
TL;DR: The evidence suggests that the actin mRNA leader sequence is acquired from this novel nucleotide transcript by an intermolecular trans-splicing mechanism.
612 citations
Cites background from "A unique cap(m7GpppXm)-dependent in..."
...It has been known for some time that influenza virus recruits Y-capped oligonucleotides from host mRNAs as primers for viral transcription (Plotch et al., 1981; Lamb and Choppin, 1983)....
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TL;DR: The purpose of this review is to illustrate using the influenza virus NP as a well-studied example that the molecule is much more than a structural RNA-binding protein, but also functions as a key adapter molecule between virus and host cell processes.
Abstract: All viruses with negative-sense RNA genomes encode a single-strand RNA-binding nucleoprotein (NP). The primary function of NP is to encapsidate the virus genome for the purposes of RNA transcription, replication and packaging. The purpose of this review is to illustrate using the influenza virus NP as a well-studied example that the molecule is much more than a structural RNA-binding protein, but also functions as a key adapter molecule between virus and host cell processes. It does so through the ability to interact with a wide variety of viral and cellular macromolecules, including RNA, itself, two subunits of the viral RNA-dependent RNA polymerase and the viral matrix protein. NP also interacts with cellular polypeptides, including actin, components of the nuclear import and export apparatus and a nuclear RNA helicase. The evidence for the existence of each of these activities and their possible roles in transcription, replication and intracellular trafficking of the virus genome is considered.
547 citations
Additional excerpts
...2a) (Plotch et al., 1981)....
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References
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TL;DR: Thin-layer separation methods for nucleic acid derivatives that are found effective in laboratory are described, including PEI-cellulose anion-exchange layers, which afford particularly sharp and highly reproducible separations of nucleotides.
Abstract: Publisher Summary The chapter describes thin-layer separation methods for nucleic acid derivatives that are found effective in laboratory. Thin-layer methods are developed for the separation and quantitative determination of nucleic acid bases, nucleosides, and nucleotides. The main advantages of thin-layer methods are sharpness of resolution, great sensitivity, simplicity, and speed. Two-dimensional anion exchange thin-layer chromatography allows resolving complex mixtures of nucleotides that are difficult to separate on paper or on a single column. Layers of the binder-free cellulose powder MN 3002 are well suited for qualitative and quantitative work. Avicel-cellulose powder is also used. A multitude of cation- and anion-exchange celluloses for thin-layer chromatography is commercially available. PEI-cellulose anion-exchange layers afford particularly sharp and highly reproducible separations of nucleotides, if they are prepared in the laboratory from unmodified cellulose and poly (ethyleneimine). For quantitative assays of bases and nucleosides, compounds are transferred from the layer to a paper wick, eluted from the paper, and measured spectrophotometrically. In combination with the quantitative techniques described, chromatography on PEI-cellulose layers are used to assay incubation mixtures and biological extracts. Oligonucleotides are separated by thin-layer chromatography or thin-layer electrophoresis or by two-dimensional combination of these methods.
513 citations
TL;DR: Reovirus mRNAs with 5′-terminal m7GppPGm or GpppG are more stable than mRNA containing unblocked ppG 5′ -ends when injected into Xenopus laevis oocytes or incubated in cell-free protein synthesising extracts of wheat germ and mouse L cells.
Abstract: Reovirus mRNAs with 5'terminal m7GpppGm or GpppG are more stable than mRNA containing unblocked ppG 5'-ends when injected into Xenopus laevis oocytes or incubated in cell-free protein synthesising extracts of wheat germ and mouse L cells. The greater stability of mRNA with blocked 5' termini is not dependent upon translation but seems to result from protection against 5'-exonucleolytic degradation.
489 citations
TL;DR: Under denaturing conditions of sodium dodecyl sulfate-polyacrylamide gel electrophoresis two majorpolypeptides were detected in purified enzyme preparations and suggested they were polypeptide components of the 127,000 molecular weight enzyme system.
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TL;DR: The method has been applied to the complete separation of RNA fractions obtained after a preliminary gel electrophoresis of partial enzymic digests of 32P-labeled bacteriophage RNA.
327 citations
TL;DR: The recently discovered noncontiguous sequences in eukaryotic DNA that encode messenger RNA may reflect an ancient, rather than a new, distribution of information in DNA and that eukARYotes evolved independently of prokaryotes.
Abstract: The differences in the biochemistry of messenger RNA formation in eukaryotes compared to prokaryotes are so profound as to suggest that sequential prokaryotic to eukaryotic cell evolution seems unlikely. The recently discovered noncontiguous sequences in eukaryotic DNA that encode messenger RNA may reflect an ancient, rather than a new, distribution of information in DNA and that eukaryotes evolved independently of prokaryotes.
296 citations