Topic
RNA-dependent RNA polymerase
About: RNA-dependent RNA polymerase is a research topic. Over the lifetime, 13904 publications have been published within this topic receiving 767954 citations. The topic is also known as: RdRp & RNA replicase.
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TL;DR: No strict correlation exists between enzyme sensitivity and MIC values, since inhibition of RNA synthesis does not always show up to the same extent in the two different test systems used for the determination of these values.
Abstract: Rifampin specifically inhibits bacterial RNA polymerase, the enzyme responsible for DNA transcription, by forming a stable drug-enzyme complex with a binding constant of 10(-9) M at 37 C. The corresponding mammalian enzymes are not affected by rifampin. Bacterial resistance to rifampin is caused by mutations leading to a change in the structure of the beta subunit of RNA polymerase. Such resistance is not an all-or-nothing phenomenon; rather, a large number of RNA polymerases with various degrees of sensitivity to rifampin have been found. No strict correlation exists between enzyme sensitivity and MIC values, since inhibition of RNA synthesis does not always show up to the same extent in the two different test systems used for the determination of these values.
345 citations
TL;DR: Nsp1 induced RNA cleavage in templates carrying the internal ribosome entry site (IRES) from encephalomyocarditis virus, but not in those carrying IRES elements from hepatitis C or cricket paralysis viruses, demonstrating that the nsp1-induced RNA modification was template-dependent.
Abstract: Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression, including type I interferon production, by promoting host mRNA degradation and inhibiting host translation, in infected cells. We present evidence that nsp1 uses a novel, two-pronged strategy to inhibit host translation and gene expression. Nsp1 bound to the 40S ribosomal subunit and inactivated the translational activity of the 40S subunits. Furthermore, the nsp1-40S ribosome complex induced the modification of the 5' region of capped mRNA template and rendered the template RNA translationally incompetent. Nsp1 also induced RNA cleavage in templates carrying the internal ribosome entry site (IRES) from encephalomyocarditis virus, but not in those carrying IRES elements from hepatitis C or cricket paralysis viruses, demonstrating that the nsp1-induced RNA modification was template-dependent. We speculate that the mRNAs that underwent the nsp1-mediated modification are marked for rapid turnover by the host RNA degradation machinery.
344 citations
TL;DR: In yeast hybrids naturally form at many loci in wild-type cells, but are removed by two evolutionarily conserved RNase H enzymes, indicating that RNA:DNA hybrids are a potent source for changing genome structure.
344 citations
TL;DR: A strategy used by the 2009 H1N1 influenza A virus to acquire second-site suppressor mutations in its PB2 polymerase subunit is revealed and other pathways by which avian and swine-origin viruses may evolve to enhance replication, and potentially pathogenesis, in humans are identified.
Abstract: Transmission of influenza viruses into the human population requires surmounting barriers to cross-species infection. Changes in the influenza polymerase overcome one such barrier. Viruses isolated from birds generally contain polymerases with the avian-signature glutamic acid at amino acid 627 in the PB2 subunit. These polymerases display restricted activity in human cells. An adaptive change in this residue from glutamic acid to the human-signature lysine confers high levels of polymerase activity in human cells. This mutation permits escape from a species-specific restriction factor that targets polymerases from avian viruses. A 2009 swine-origin H1N1 influenza A virus recently established a pandemic infection in humans, even though the virus encodes a PB2 with the restrictive glutamic acid at amino acid 627. We show here that the 2009 H1N1 virus has acquired second-site suppressor mutations in its PB2 polymerase subunit that convey enhanced polymerase activity in human cells. Introduction of this polymorphism into the PB2 subunit of a primary avian isolate also increased polymerase activity and viral replication in human and porcine cells. An alternate adaptive strategy has also been identified, whereby introduction of a human PA subunit into an avian polymerase overcomes restriction in human cells. These data reveal a strategy used by the 2009 H1N1 influenza A virus and identify other pathways by which avian and swine-origin viruses may evolve to enhance replication, and potentially pathogenesis, in humans.
343 citations
TL;DR: This chapter discusses the initiation of transcription of protein-coding genes in the study of eukaryotic RNAPII, as features such as function and subunit structure have been highly conserved.
Abstract: Publisher Summary This chapter discusses the initiation of transcription of protein-coding genes. The RNA polymerase II(RNAPII) of the yeast Saccharomyces cerevisiae has been a useful prototype in the study of eukaryotic RNAPII, as features such as function and subunit structure have been highly conserved. The yeast RNAPII is composed of 11 polypeptides with apparent masses ranging from 220 to 10 kDa. This is in contrast to eukaryotic cells, which contain three distinct RNA polymerases, each containing from 8 to 14 polypeptides and responsible for transcribing its own set of genes: RNA polymerase I (RNAPI), which transcribes ribosomal RNA; RNAPII, the RNA polymerase of protein-coding, or class 11, genes; and RNAPIII, which transcribes 5-S rRNA and tRNA genes. In this chapter, only RNAPII is discussed, and only as it pertains to transcription initiation.
342 citations