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Vicens, Q.

Publications and source records attributed to Vicens, Q..

2 recordsLinked to original sources

Pervasiveness of exoribonuclease-resistant RNAs in plant viruses suggests new roles for these conserved RNA structures

Exoribonuclease-resistant RNAs (xrRNAs) are discrete folded RNA elements that block the processive degradation of RNA by exoribonucleases. xrRNAs found in the 3' untranslated regions (UTRs) of animal-infecting flaviviruses and in all three members of the plant-infecting Dianthovirus adopt a complex ring-like fold that blocks the exoribonuclease; this ability gives rise to viral non-coding subgenomic RNAs. The degree to which these folded RNA elements exist in other viruses and in diverse contexts has been unclear. Using computational tools and biochemical assays, we discovered that xrRNA elements are widely found in viruses belonging to the Tombusviridae and Luteoviridae families of plant-infecting RNA viruses, demonstrating their importance and widespread utility. Unexpectedly, many xrRNAs are located in intergenic regions rather than in the 3UTR and some are associated with the 5' ends of subgenomic RNAs with protein-coding potential, suggesting that xrRNAs with similar scaffolds are involved in the maturation or maintenance of diverse subgenomic RNAs, not just the ones generated from the 3'UTR.

microbiology

Structure-activity relationship of flavin analogs that target the FMN riboswitch

The flavin mononucleotide (FMN) riboswitch is an emerging target for the development of novel RNA-targeting antibiotics. We previously discovered an FMN derivative --5FDQD-- that protects mice against diarrhea-causing Clostridium difficile bacteria. Here, we present the structure-based drug design strategy that led to the discovery of this fluoro-phenyl derivative with antibacterial properties. This approach involved the following stages: (1) structural analysis of all available free and bound FMN riboswitch structures; (2) design, synthesis and purification of derivatives; (3) in vitro testing for productive binding using two chemical probing methods; (4) in vitro transcription termination assays; (5) resolution of the crystal structures of the FMN riboswitch in complex with the most mature candidates. In the process, we delineated principles for productive binding to this riboswitch, thereby demonstrating the effectiveness of a coordinated structure-guided approach to designing drugs against RNA.\n\nGRAPHICAL ABSTRACT\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC=\"FIGDIR/small/389148_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (41K):\norg.highwire.dtl.DTLVardef@f59798org.highwire.dtl.DTLVardef@1b38b02org.highwire.dtl.DTLVardef@6b50faorg.highwire.dtl.DTLVardef@1915fc4_HPS_FORMAT_FIGEXP M_FIG Exploring the chemical structure landscape of FMN riboswitch binders.\n\nC_FIG

biochemistry