It has been proposed that ribosomes possess an intrinsic ability to regulate translation through the differential expression, recruitment or modification of specific ribosomal proteins. Through this “ribosome specialization,” changes in ribosome composition and subsequent recognition of specific RNA elements may extend an additional level of control over protein synthesis. Virus infection may provide a novel context by which to study ribosome specialization, where it has been shown that specific ribosomal proteins are required for the selective translation of viral mRNA. For example, in Cricket paralysis virus- or hepatitis C virus-infected cells, depletion of ribosomal protein S25 (RPS25) impairs translation of viral but not host transcripts.
Recent data from our lab shows that Vaccinia virus (VacV), a large DNA virus of the poxvirus family, also requires specific ribosomal proteins for viral mRNA translation. One of these is Receptor for Activated C Kinase 1 (RACK1), a scaffolding protein that associates with the 40S subunit near the mRNA exit channel. RACK1 is now recognized to be a core 40S ribosomal subunit protein, and is emerging as a key regulator of translation. Using a variety of biochemical approaches, we have found that a VacV kinase phosphorylates unique sites in RACK1 and thereby selectively enhances translation of viral mRNAs, which contain unusual polyA leader elements. My thesis project aims to determine how VacV-specialized ribosomes are assembled and function to promote translation of viral versus host transcripts to facilitate infection.