Our laboratory studies how cells recognize and degrade aberrant, damaged, unneeded and potentially harmful RNAs. Most cellular RNA does not code for proteins, and truncated, misfolded and aberrant noncoding RNAs can accumulate as a result of mutations, transcriptional errors and processing mistakes. Also, as retrotransposon-derived sequences make up much of mammalian genomes, transcripts from these elements may need to be recognized and degraded. Finally, certain types of environmental stress, such as exposure to oxidants and ultraviolet light, can result in RNA damage.
One pathway that we study involves a protein called the Ro 60 kDa autoantigen. Ro60 was discovered because it is a major target of the immune system in patients with the rheumatic diseases systemic lupus erythematosus and Sjogren’s syndrome. Ro60 is present in many animal cells and also in ~5% of sequenced bacterial genomes. In both mammalian cells and bacteria, Ro60 is important for survival after UV irradiation. Our collaboration with the laboratory of Karin Reinisch revealed that Ro60 is shaped like a donut with a central hole and that Ro60 binds the ends of misfolded and defective RNAs inside its central cavity. By studying Ro60 in bacteria, the laboratory discovered recently that this protein is tethered by a noncoding "Y RNA" to a ring-shaped ribonuclease, forming a RNA degradation machine specialized for degrading structured RNA. We are now characterizing additional roles for the Ro60 protein and Y RNAs in both mammalian cells and bacteria.
By studying the packaging of host RNAs by retroviruses, we recently discovered a new ncRNA surveillance pathway in mammalian cells. In this pathway, newly synthesized noncoding RNAs are exported to the cytoplasmic for degradation. We are now characterizing additional components of this pathway. We are also determining how packaging of newly synthesized host ncRNAs contributes to the assembly and infectivity of retroviruses.