Cellular RNA molecules undergo complex folding transitions to form specific, biologically active, three-dimensional structures. A persistent and poorly explained observation is that many RNAs fold very slowly, on timescales requiring minutes or longer. Slow folding ultimately governs the rate at which an RNA can perform its biological function.
In work reported in PNAS, Stefanie Mortimer in the Weeks Lab used time-resolved SHAPE chemistry to show that slow folding at a single nucleotide in the unusual C2'-endo conformation constitutes the rate-determining step for folding a large 50 kDa RNA. Nucleotides in the C2'-endo conformation are relatively rare but are highly overrepresented in functionally critical RNA motifs. This work thus identifies a surprisingly simple, but likely ubiquitous, mechanism for controlling biological processes involving RNA.
As reported as the cover story of the journal Nature, a team lead by UNC chemists reports a model for the structure of an entire HIV genome. Single-stranded, ribbon-like, RNA genomes - like that in HIV - fold back on themselves to make molecular objects, which often have critical regulatory roles.
Kevin Weeks' laboratory focuses on the chemical and structural biology of RNA. Dr. Weeks thought that technologies created in his lab could help the HIV research community and led the study to solve the structure of an entire HIV-1 genome. The lab collaborated with the National Cancer Institute and UNC virologists.
The new results show that the HIV RNA genome contains numerous RNA structures that influence how HIV proteins are made and how the virus escapes detection by the human host. HIV genome structure appears to be so extensive as to constitute another level of the genetic code. Insights gleaned from this work also hold substantial promise for developing new antiviral therapeutics.