The Structure of a Rigorously Conserved RNA Element within the SARS Virus Genome

We have solved the three-dimensional crystal structure of the stem-loop II motif (s2m) RNA element of the SARS virus genome to 2.7-Å resolution. SARS and related coronaviruses and astroviruses all possess a motif at the 3′ end of their RNA genomes, called the s2m, whose pathogenic importance is inferred from its rigorous sequence conservation in an otherwise rapidly mutable RNA genome. We find that this extreme conservation is clearly explained by the requirement to form a highly structured RNA whose unique tertiary structure includes a sharp 90° kink of the helix axis and several novel longer-range tertiary interactions. The tertiary base interactions create a tunnel that runs perpendicular to the main helical axis whose interior is negatively charged and binds two magnesium ions. These unusual features likely form interaction surfaces with conserved host cell components or other reactive sites required for virus function. Based on its conservation in viral pathogen genomes and its absence in the human genome, we suggest that these unusual structural features in the s2m RNA element are attractive targets for the design of anti-viral therapeutic agents. Structural genomics has sought to deduce protein function based on three-dimensional homology. Here we have extended this approach to RNA by proposing potential functions for a rigorously conserved set of RNA tertiary structural interactions that occur within the SARS RNA genome itself. Based on tertiary structural comparisons, we propose the s2m RNA binds one or more proteins possessing an oligomer-binding-like fold, and we suggest a possible mechanism for SARS viral RNA hijacking of host protein synthesis, both based upon observed s2m RNA macromolecular mimicry of a relevant ribosomal RNA fold

The Scientific Foundations of Forecasting Magnetospheric Space Weather

The magnetosphere is the lens through which solar space weather phenomena are focused and directed towards the Earth. In particular, the non-linear interaction of the solar wind with the Earth's magnetic field leads to the formation of highly inhomogenous electrical currents in the ionosphere which can ultimately result in damage to and problems with the operation of power distribution networks. Since electric power is the fundamental cornerstone of modern life, the interruption of power is the primary pathway by which space weather has impact on human activity and technology. Consequently, in the context of space weather, it is the ability to predict geomagnetic activity that is of key importance. This is usually stated in terms of geomagnetic storms, but we argue that in fact it is the substorm phenomenon which contains the crucial physics, and therefore prediction of substorm occurrence, severity and duration, either within the context of a longer-lasting geomagnetic storm, but potentially also as an isolated event, is of critical importance. Here we review the physics of the magnetosphere in the frame of space weather forecasting, focusing on recent results, current understanding, and an assessment of probable future developments.Peer reviewe