The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5′ end, the ribosomal frameshift segment and the 3′-untranslated region (3′-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention.
A novel, extremely thermoacidophilic, obligately chemolithotrophic archaeon (strain JP7T) was isolated from a solfatara on Lihir Island, Papua New Guinea. Cells of this organism were non-motile, Gram-negative staining, irregular-shaped cocci, 0.5–1.5 μm in size, that grew aerobically by oxidation of sulfur, Fe2+ or mineral sulfides. Cells grew anaerobically using Fe3+ as a terminal electron acceptor and H2S as an electron donor but did not oxidize hydrogen with elemental sulfur as electron acceptor. Strain JP7T grew optimally at 74 °C (temperature range 45–83 °C) and pH 0.8–1.4 (pH range 0.35–3.0). On the basis of 16S rRNA gene sequence similarity, strain JP7T was shown to belong to the Sulfolobaceae, being most closely related to the type strains of Acidianus ambivalens (93.7 %) and Acidianus infernus (93.6 %). Cell-membrane lipid structure, DNA base composition and 16S rRNA gene sequence similarity data support the placement of this strain in the genus Acidianus. Differences in aerobic and anaerobic metabolism, temperature and pH range for growth, and 16S rRNA gene sequence differentiate strain JP7T from recognized species of the genus Acidianus, and an emendation of the description of the genus is proposed. Strain JP7T is considered to represent a novel species of the genus Acidianus, for which the name Acidianus sulfidivorans sp. nov. is proposed. The type strain is JP7T (=DSM 18786T=JCM 13667T).
Nuclear export of influenza A virus (IAV) mRNAs occurs through the nuclear pore complex (NPC). Using the Auxin-Induced Degron (AID) system to rapidly degrade proteins, we show that among the nucleoporins localized at the nucleoplasmic side of the NPC, TPR is the key nucleoporin required for nuclear export of influenza virus mRNAs. TPR recruits the TRanscription and EXport complex (TREX)−2 to the NPC for exporting a subset of cellular mRNAs. By degrading components of the TREX-2 complex (GANP, Germinal-center Associated Nuclear Protein; PCID2, PCI domain containing 2), we show that influenza mRNAs require the TREX-2 complex for nuclear export and replication. Furthermore, we found that cellular mRNAs whose export is dependent on GANP have a small number of exons, a high mean exon length, long 3’ UTR, and low GC content. Some of these features are shared by influenza virus mRNAs. Additionally, we identified a 45 nucleotide RNA signal from influenza virus HA mRNA that is sufficient to mediate GANP-dependent mRNA export. Thus, we report a role for the TREX-2 complex in nuclear export of influenza mRNAs and identified RNA determinants associated with the TREX-2-dependent mRNA export.
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