A major challenge in understanding the structure of large RNAs — including the genomes of RNA viruses — is discovering where the functionally critical parts lie. One structure, called an RNA pseudoknot, tends to occur in key areas that affect viral replication and other activities and could make strong drug targets. However, pseudoknots are hard to predict in RNA secondary structures and existing modeling techniques are generally not able to detect them reliably.
In work published in the Proc. Natl. Acad. Sci. USA, Christine Hajdin in the Weeks lab melded experimental and computational techniques to identify pseudoknots with a high degree of accuracy. She initially applied her approach to a set of 21 challenging RNAs of up to 530 nucleotides in size. Christine's approach recovered 93% of known RNA base pairs and all pseudoknots in well-folded RNAs were identified. More recently, Christine's approach has been used to successfully predict functionally important pseudoknots, "golden RNA needles", in the HIV virus RNA genome "haystack."
Work entirely designed, implemented, and interpreted by UNC undergraduates has been published in Biochemistry and is highlighted on the journal web page. Many viruses encode their genetic information in RNA molecules and these RNAs can have complex structures that are essential for efficient replication. The all-undergraduate team developed a model for the genome of the satellite tobacco mosaic virus, which is roughly the "hydrogen atom" of RNA viruses.
The UNC undergraduates discovered that the RNA genome has a complex higher-order structure with three domains, each of which corresponds to an essential viral function. This work is likely to broadly inform our understanding of the role of genome structure in the infectivity and pathogenesis of many RNA viruses, including those that infect humans.
The work was carried out as part of the UNC Undergraduate Transcriptome Project, an NSF-funded program developed in the Weeks Laboratory, designed to help undergraduates explore their potential for independent creativity, to fuel their passion for science, and to be a model for engaging undergraduates in a research university.