Research: Trimethylguanosine synthase (TGS1) plays an essential role in RNA biology, where it catalyzes hypermethylation of the 7-methylguanosine cap to 2,2,7-
trimethylguanosine cap. This epitranscriptomic modification licenses select host
and viral mRNAs for a specialized translation pathway that bypasses mTOR
inhibition. While the importance of this pathway is only starting to be recognized,
it has been implicated in important diseases including cancer and HIV-1 infection.
Notably, loss of TGS1 results in a 1000-fold restriction of HIV-1. Despite the
importance of this pathway, there remain significant gaps in knowledge. My work
aims to: a) define viral and host RNA and protein determinants of mRNA cap hypermethylation; and b) describe the functional consequences of HIV-1 cap
hypermethylation that antagonize host restriction.
