Molecular mechanisms underpinning RNA-controlled self-assembly of multi-segmented viral genomes.
Rotaviruses are highly contagious pathogens that mainly infect children. Most children will be infected at least once by the age of five, and that means there are a huge number of cases every year – estimated at over 114 million – with upwards of 200,000 deaths. During rotavirus replication, RNA segments are copied many times. It is not clear how rotaviruses 'count' up to 11 so that each new virus acquires a single copy of each segment. Despite the importance of understanding the molecular basis of segmented RNA genome packaging, there is very little knowledge of how eleven distinct RNAs are selected in rotaviruses. Our goal is to find out how rotaviruses select the right gene segments by exploring their individual structures and how they interact with each other. To achieve this, we use a combination of single-molecule fluorescence techniques, RNA imaging and structure probing.
Research objectives
-
Understand the roles of viral RNA chaperones in the process of RNA assembly during viral infection.
-
Identify RNA sequences that mediate RNA genome assembly.
-
Uncover the molecular architecture of viral RNA assembly sites and identify their essential components.
-
Dissect the molecular mechanisms underlying the formation of viral factories and their molecular selectivity.
Key publications
Bravo JPK, Bartnik K, Venditti L, Acker J, Gail EH, Colyer A, Davidovich C, Lamb DC, Tuma R, Calabrese AN, Borodavka A (2021). Structural basis of rotavirus RNA chaperone displacement and RNA annealing. Proc. Natl. Acad. Sci., 118:e2100198118. doi: 10.1073/pnas.2100198118
Geiger F, Acker J, Papa G, Wang X, Arter WE, Saar KL, Erkamp NA, Qi R, Bravo JPK, Strauss S, Krainer G, Burrone OR, Jungmann R, Knowles TPJ, Engelke H, Borodavka A (2021). Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses. EMBO J., e107711. doi: 10.15252/embj.2021107711
Borodavka A, Desselberger U, Patton JT (2018). Genome packaging in multi-segmented dsRNA viruses: distinct mechanisms with similar outcomes. Curr. Opin. Virol., 33(1):106-112. doi: 10.1016/j.coviro.2018.08.001
Bravo JPK, Borodavka A, Barth A, Calabrese AN, Mojzes P, Cockburn JJB, Lamb DC, Tuma R (2018). Stability of local secondary structure determines selectivity of viral RNA chaperones. Nucleic Acids Res., 46(15):7924-7937. doi: 10.1093/nar/gky394
Borodavka A, Dykeman EC, Schrimpf W, Lamb DC (2017). Protein-mediated RNA folding governs sequence-specific interactions between rotavirus genome segments. eLife, 6:e27453. doi: 10.7554/eLife.27453
Alex Borodavka