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Bonilla, S.

Publications and source records attributed to Bonilla, S..

3 recordsLinked to original sources

An A-rich linker between dengue virus tandem xrRNAs facilitates functional coordination

Orthoflaviviruses use programmed resistance to host 5' to 3' exoribonucleases to produce subgenomic flaviviral RNAs (sfRNAs) during infection. This resistance is conferred by exoribonuclease-resistant RNA (xrRNA) structures that often occur in tandem and whose function can be coupled. In dengue virus serotype 2 (DENV2) this coupling results in changing patterns of sfRNA identity and abundance linked to the ability of the virus to adapt to host vs. vector infections. The physical basis of this coupling was unknown. Using a combination of virology, biochemistry, bioinformatics, structural biology, and biophysics, we explored the structural and sequence determinants of tandem xrRNA coupling in DENV2. We discovered that the spatial proximity, order, and structural integrity of the tandem xrRNAs are all important for coupling. Furthermore, an unpaired A-rich linker that lies between the two xrRNAs is essential in stabilizing a specific structure that correlates to coupling. This A-rich sequence likely forms tertiary contacts with an adjacent stem-loop structure to form a physical bridge between the two xrRNAs, a finding that is supported by a mid-resolution cryoEM map of the DENV2 tandem xrRNAs. Disruption of the structure of this bridge by mutation changes the relative orientation or spacing between the tandem xrRNAs, which is correlated to their functional coupling. These findings provide an explanation for the coupling between tandem xrRNAs and suggests new mechanistic hypotheses. IMPORTANCEDengue virus (DENV) generates non-coding subgenomic flaviviral RNAs (sfRNAs) that affect several cellular pathways and are important for successful infection. These sfRNAs are formed by structured RNA elements in the viral genome called exoribonuclease-resistant RNAs (xrRNAs), which fold into a distinct three-dimensional topology to block degradation by host cell exoribonucleases and often occur in tandem. Specific patterns of sfRNAs made during infection are important for host vs. vector fitness, and in DENV2 this pattern depends on functional coupling between tandem xrRNAs. However, the source of this functional coupling was unknown. We determined that an unpaired A-rich linker between the tandem xrRNAs is necessary for creating a structural bridge between the tandem xrRNAs. This bridge appears to favor a specific orientation between the tandem xrRNAs that is correlated to coupling and therefore to the patterns and relative abundance of sfRNAs produced during infection.

microbiology↗

A structured viral RNA uses molecular mimicry and conformational dynamics to coordinate multiple functions

Viruses require multifunctional structured RNAs to hijack their hosts biochemistry, but their mechanisms can be obscured by the difficulty of solving conformationally dynamic RNA structures. Using cryo-EM, we visualized the structure of the mysterious viral tRNA-like structure (TLS) from brome mosaic virus (BMV), which affects replication, translation, and genome encapsidation. Structures in isolation and bound to tyrosyl-tRNA synthetase (TyrRS) show that this [~]55 kDa purported tRNA mimic undergoes large conformational rearrangements to bind TyrRS in a form that differs dramatically from tRNA. Our studies reveal how viral RNAs can use a combination of static and dynamic RNA structures to bind host machinery through highly noncanonical interactions and highlights the utility of cryo-EM for visualizing small conformationally dynamic structured RNAs.

biophysics↗

Mapping the impacts of hurricanes Maria and Irma on banana production area in the Dominican Republic

Extreme weather events can have devastating impacts on agricultural systems, and the livelihoods that depend on them. Tools for rapid, comprehensive and cost-effective assessment of impacts, especially if carried out remotely, can be of great value in planning systematic recovery of production, as well as assessing risks from future events. Here, we use openly available remote sensing data to quantify the impacts of hurricanes Irma and Maria in 2017 on banana production area in the Dominican Republic -- the worlds largest producer of organic bananas. Further, we assess the risk to current production area if a similar extreme event were to re-occur. Hurricane associated damage was mapped using a simple change detection algorithm applied to Synthetic Aperture Radar (SAR) data over the three main banana growing provinces of northern Dominican Republic, i.e. Monte Cristi, Valverde and Santiago. The map of hurricane affected area was overlaid with banana plantation distributions for 2017 and 2019 that were mapped (accuracy = 99.8%) using a random forest classifier, and a combination of SAR and multi-spectral satellite data. Our results show that 11.35% of banana plantation area was affected by hurricane damage in 2017. Between 2017 and 2019, there was a high turnover of plantation area, but with a net gain of 10.8%. However, over a quarter (26.9%) of new plantation area spatially overlapped with regions which had seen flooding or damage from hurricanes in 2017. Our results indicate that banana production systems in northern Dominican Republic saw extensive damage in the aftermath of hurricanes Irma and Maria. While production area has recovered since then, a substantial proportion of new plantations, and a greater fraction of production area in general, occur at locations at risk from future extreme events.

ecology↗