An overarching theme of our research is the interface of cellular post-transcriptional mechanisms with retroviruses that cause cancer and AIDS.
Discovery is where this story begins, of a unique translation activation mechanism that is reserved for retroviruses and a select cohort of cellular mRNAs. By combining genetic and RNA structural analysis with proteomics and biophysical approaches, we discovered a class of cognate RNA elements that tightly regulate whether or not an mRNA is successful as template for protein synthesis.
Our research elucidated basic amino acid residues in the RNA binding protein intercalate RNA secondary structure at the 5’ end of the transcript, tethering catalytic activity that was triggered by ATP binding.

Like a knife loosening a complicated knot, physical change to the ribonucleoprotein complex yielded a less complex structure that became engaged with scanning ribosomes. Simply observed by collection at the bottom a sucrose gradient, the RNP is heavy polysomes, capture by mRNA template of many ribosomes.
Historically, a longstanding issue in virology is how a viral RNA genome of 9000 bases proves sufficient to generate a multi-component virion and genomic RNP, with capacity for infection and spread in animal and human populations. The answers have been debated since the 1970’s, and the solution lays in the RNA structures we have shown are magnets to nucleate RNP components responsible for protein synthesis.