scholarly journals Truncated yet functional viral protein produced via RNA polymerase slippage implies underestimated coding capacity of RNA viruses

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yuka Hagiwara-Komoda ◽  
Sun Hee Choi ◽  
Masanao Sato ◽  
Go Atsumi ◽  
Junya Abe ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Viral Protein ◽  
Rna Viruses ◽  
Coding Capacity ◽  
Polymerase Slippage

scholarly journals Protein Nucleotidylylation in +ssRNA Viruses

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1549
Author(s):  
Alice-Roza Eruera ◽  
Alice M. McSweeney ◽  
Geena M. McKenzie-Goldsmith ◽  
Vernon K. Ward
Keyword(s):  
Life Cycle ◽  
Rna Polymerase ◽  
Viral Replication ◽  
Viral Protein ◽  
Rna Viruses ◽  
Replication Initiation ◽  
Genome Replication ◽  
Rna Dependent Rna Polymerase ◽  
Nucleotidyl Transferase ◽  
Initiation Of Translation

Nucleotidylylation is a post-transcriptional modification important for replication in the picornavirus supergroup of RNA viruses, including members of the Caliciviridae, Coronaviridae, Picornaviridae and Potyviridae virus families. This modification occurs when the RNA-dependent RNA polymerase (RdRp) attaches one or more nucleotides to a target protein through a nucleotidyl-transferase reaction. The most characterized nucleotidylylation target is VPg (viral protein genome-linked), a protein linked to the 5′ end of the genome in Caliciviridae, Picornaviridae and Potyviridae. The nucleotidylylation of VPg by RdRp is a critical step for the VPg protein to act as a primer for genome replication and, in Caliciviridae and Potyviridae, for the initiation of translation. In contrast, Coronaviridae do not express a VPg protein, but the nucleotidylylation of proteins involved in replication initiation is critical for genome replication. Furthermore, the RdRp proteins of the viruses that perform nucleotidylylation are themselves nucleotidylylated, and in the case of coronavirus, this has been shown to be essential for viral replication. This review focuses on nucleotidylylation within the picornavirus supergroup of viruses, including the proteins that are modified, what is known about the nucleotidylylation process and the roles that these modifications have in the viral life cycle.

scholarly journals The Yeast Transcription Terminator for RNA Polymerase I Is Designed to Prevent Polymerase Slippage

1996 ◽  
Vol 271 (27) ◽  
pp. 16104-16110 ◽  
Author(s):  
Shin Wu Jeong ◽  
Walter H. Lang ◽  
Ronald H. Reeder
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase I ◽  
Transcription Terminator ◽  
Polymerase I ◽  
Polymerase Slippage

scholarly journals Design and Synthesis of Antiviral Iminoribitol C-Nucleosides

2021 ◽  
Author(s):  
◽  
Ye Li
Keyword(s):  
Antiviral Activity ◽  
Rna Polymerase ◽  
Nucleoside Analogue ◽  
Rna Viruses ◽  
Active Form ◽  
Building Blocks ◽  
The Body ◽  
Nucleoside Analogues ◽  
Federal Drug Administration ◽  
Pharmacologically Active

<p>Infections caused by RNA viruses, such as Ebola and Zika, continue to exist worldwide as significant public health problems. In response to the urgent need for safer and more efficacious treatment options to treat infections caused by RNA viruses, the pharmaceutical and biotechnology industries have devoted significant efforts over the last two decades to discovering and developing new antiviral agents. One such antiviral, Sofosbuvir®, was approved by the US Federal Drug Administration (FDA) in 2014 and has revolutionized the treatment of Hepatitis-C. Sofosbuvir® was the second largest selling drug in the world in 2016 and in just twenty-one months Gilead reported sales worth $26.6 billion USD.The strategy of using nucleoside analogues to inhibit viral RNA dependent RNA polymerase(RdRp)has been pursued since the 1970s, and exemplified bythe discovery and development of ribavirin. The natural substrates of RNA polymerases are nucleoside triphosphates and often the efficacy of nucleoside analogues as antivirals are dependent on their ability to be converted by the host or virus to mono-, di-, and ultimately tri-phosphate analogues which block the active site of RNA polymerase as an analogue of the substrate causing chain termination. Recently Biocryst Pharmaceuticals (Biocryst) described the anti-viral properties of Immucillin-A (Galidesivir), an iminoribitol based nucleoside analogue, which was found to have broad spectrum antiviral activity especially against RNA viruses including Ebola. Researchers at the Ferrier Research Institute (Ferrier) have synthesizedan analogue of Immucillin-A, 8-aza-Immucillin-A (AIA) which shows comparable activityto Immucillin-A, in anti-viral screens against Ebola, and this antiviral activity forms part of a US patent application. The Ferrier is keen to further exemplify this compound class through the synthesis of analogues of both Immucillin-A and AIA as well as improve the overall synthesis of the lead compound AIA.Included as part of this study is the synthesis of pro-drugs of these iminoribitol based nucleoside analogues. Prodrugs are metabolized inside the body and are often converted to the corresponding pharmacologically active form. In general, prodrug strategies have improved the bioavailability and efficacy of many drugs. In particular, prodrugs strategies involving nucleoside analogue antivirals, which target RNA polymerase, have been particularly effective as they ensure conversion to the monophosphate in vivo. Conversion to the 5’-monophosphate form of a nucleoside analogue is the rate limiting step to the inhibition of the RNA polymerase –prior to its conversion to the triphosphateanalogue. The prodrug is effectively a protected monophosphate, and is then readily converted to monophosphate by the host and then onto the di-and tri-phosphate by kinases in both the host and virus. ProTide prodrugs, such as Sofosbuvir® provide a verified strategy for improving anti-viral activity and hence our desire to synthesize pro-drugs of all our iminoribitol based nucleoside analogues. This research thesis also involved repeating the known synthesis of the Immucillins, in particular, Immucillin-H (Forodesine), which requires in excess of 20 linear synthetic steps to make. The linear synthetic route to Immucillin-H was used instead of the more convenient convergent method developed by the Ferrier as several key synthetic intermediates in this progress were utilized in the attempted synthesis of some of the planned nucleoside analogues of AIA. As part of this work the candidate learned aspects of scaling up chemical reactions andthe critical analysis of both reaction hazards and reagent compatibilities at scale. Where possible and given the number of synthetic steps involved the candidate was also interested in improving the yields of the building blocks involved in the synthesis of the Immucillins with limited success.</p>

scholarly journals Single Passage of Human Metapneumovirus in LLC-MK2 Cells Does Not Affect Viral Protein-Coding Capacity

2018 ◽  
Vol 6 (21) ◽  
Author(s):  
Simon Loevenich ◽  
Aleksandr Ianevski ◽  
Eneli Oitmaa ◽  
Denis E. Kainov ◽  
Marit W. Anthonsen
Keyword(s):  
Amino Acid ◽  
Viral Protein ◽  
Complete Genome ◽  
Human Metapneumovirus ◽  
Amino Acid Sequences ◽  
Paired Comparisons ◽  
Genome Sequences ◽  
Protein Coding ◽  
Single Passage ◽  
Coding Capacity

ABSTRACT Here, we report the complete genome sequences of human metapneumovirus (HMPV) prior to and after passaging in LLC-MK2 cells. Paired comparisons of the 13,335-nucleotide genomes revealed that the virus acquired the T10736C transition in its genome, which did not affect the amino acid sequences of HMPV proteins.

Replication of RNA viruses: Structure of a 6 s RNA synthesized by the Qβ RNA polymerase

1972 ◽  
Vol 71 (3) ◽  
pp. 657-670 ◽  
Author(s):  
Carol L. Prives ◽  
Philip M. Silverman
Keyword(s):  
Rna Polymerase ◽  
Rna Viruses

scholarly journals Transcribing paramyxovirus RNA polymerase engages the template at its 3′ extremity

2006 ◽  
Vol 87 (3) ◽  
pp. 665-672 ◽  
Author(s):  
Samuel Cordey ◽  
Laurent Roux
Keyword(s):  
Rna Polymerase ◽  
Transcription Initiation ◽  
Fluorescent Protein ◽  
Sendai Virus ◽  
Rna Viruses ◽  
Mrna Transcription ◽  
Gfp Expression ◽  
Rnase Protection ◽  
Virus Rna ◽  
Green Fluorescent

For the non-segmented, negative-stranded RNA viruses, the mechanism controlling transcription or replication is still a matter of debate. To gain information about this mechanism and about the nature of the RNA polymerase involved, the length of an intervening sequence separating the 3′ end of Sendai virus minigenomes and a downstream transcription-initiation signal was increased progressively. It was found that transcription, as measured by green fluorescent protein (GFP) expression, decreased progressively in proportion to the increase in length of the intervening sequence. GFP expression correlated well with the levels of GFP mRNA in the cells, as measured by quantitative primer extension and by RNase protection. Thus, mRNA transcription was inversely proportional to the length of the inserted sequence. These data are evidence that the RNA polymerase initiating transcription at the downstream transcription signal somehow sees the distance separating this signal and the template 3′ extremity. Implication of this observation for the nature of the Sendai virus RNA polymerase and for the mechanism by which it synthesizes mRNAs or replication products is presented.

scholarly journals RNA Polymerase Slippage as a Mechanism for the Production of Frameshift Gene Products in Plant Viruses of the Potyviridae Family

2015 ◽  
Vol 89 (13) ◽  
pp. 6965-6967 ◽  
Author(s):  
Bernardo Rodamilans ◽  
Adrian Valli ◽  
Ares Mingot ◽  
David San León ◽  
David Baulcombe ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Plant Viruses ◽  
Gene Products ◽  
Polymerase Slippage

scholarly journals Discovery of divided RdRp sequences and a hitherto unknown genomic complexity in fungal viruses

2020 ◽  
Author(s):  
Yuto Chiba ◽  
Takashi Yaguchi ◽  
Syun-ichi Urayama ◽  
Daisuke Hagiwara
Keyword(s):  
Rna Polymerase ◽  
Rna Viruses ◽  
Current Knowledge ◽  
Single Gene ◽  
Rna Seq ◽  
Rna Dependent Rna Polymerase ◽  
Independent Manner ◽  
Viral Genomes ◽  
True Diversity ◽  
Fungal Viruses

AbstractBy identifying variations in viral RNA genomes, cutting-edge metagenome technology has potential to reshape current concepts about the evolution of RNA viruses. This technology, however, cannot process low-homology genomic regions properly, leaving the true diversity of RNA viruses unappreciated. To overcome this technological limitation we applied an advanced method, Fragmented and Primer-Ligated Double-stranded (ds) RNA Sequencing (FLDS), to screen RNA viruses from 155 fungal isolates, which allowed us to obtain complete viral genomes in a homology-independent manner. We created a high-quality catalog of 19 RNA viruses (12 viral species) that infect Aspergillus isolates. Among them, nine viruses were not detectable by the conventional methodology involving agarose gel electrophoresis of dsRNA, a hallmark of RNA virus infections. Segmented genome structures were determined in 42% of the viruses. Some RNA viruses had novel genome architectures; one contained a dual methyltransferase domain and another had a separated RNA-dependent RNA polymerase (RdRp) gene. A virus from a different fungal taxon (Pyricularia) had an RdRp sequence that was separated on different segments, suggesting that a divided RdRp is widely present among fungal viruses, despite the belief that all RNA viruses encode RdRp as a single gene. These findings illustrate the previously hidden diversity and evolution of RNA viruses, and prompt reconsideration of the structural plasticity of RdRp. By highlighting the limitations of conventional surveillance methods for RNA viruses, we showcase the potential of FLDS technology to broaden current knowledge about these viruses.Author SummaryThe development of RNA-seq technology has facilitated the discovery of RNA viruses in all types of biological samples. However, it is technically difficult to detect highly novel viruses using RNA-seq. We successfully reconstructed the genomes of multiple novel fungal RNA viruses by screening host fungi using a new technology, FLDS. Surprisingly, we identified two viral species whose RNA-dependent RNA polymerase (RdRp) proteins were separately encoded on different genome segments, overturning the commonly accepted view of the positional unity of RdRp proteins in viral genomes. This new perspective on divided RdRp proteins should hasten the discovery of viruses with unique RdRp structures that have been overlooked, and further advance current knowledge and understanding of the diversity and evolution of RNA viruses.

scholarly journals Late Male-Killing Viruses in Homona magnanima Identified as Osugoroshi Viruses, Novel Members of Partitiviridae

2021 ◽  
Vol 11 ◽  
Author(s):  
Ryosuke Fujita ◽  
Maki N. Inoue ◽  
Takumi Takamatsu ◽  
Hiroshi Arai ◽  
Mayu Nishino ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Rna Polymerase ◽  
Rna Viruses ◽  
Rna Virus ◽  
Horizontal Transmission ◽  
Rna Dependent Rna Polymerase ◽  
Double Stranded Rna ◽  
First Report ◽  
Male Killing ◽  
Male Specific

Late male-killing, a male-specific death after hatching, is a unique phenotype found in Homona magnanima, oriental tea tortrix. The male-killing agent was suspected to be an RNA virus, but details were unknown. We herein successfully isolated and identified the putative male-killing virus as Osugoroshi viruses (OGVs). The three RNA-dependent RNA polymerase genes detected were phylogenetically related to Partitiviridae, a group of segmented double-stranded RNA viruses. Purified dsRNA from a late male-killing strain of H. magnanima revealed 24 segments, in addition to the RdRps, with consensus terminal sequences. These segments included the previously found male-killing agents MK1068 (herein OGV-related RNA16) and MK1241 (OGV-related RNA7) RNAs. Ultramicroscopic observation of purified virions, which induced late male-killing in the progeny of injected moths, showed sizes typical of Partitiviridae. Mathematical modeling showed the importance of late male-killing in facilitating horizontal transmission of OGVs in an H. magnanima population. This study is the first report on the isolation of partiti-like virus from insects, and one thought to be associated with late male-killing, although the viral genomic contents and combinations in each virus are still unknown.

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