Sandra L Wolin

Sandra Wolin’s laboratory studies how proteins chaperone RNA biogenesis and how defective RNAs are recognized by surveillance pathways. These pathways are of physiological and pathological relevance, as excess cellular RNAs, by activating cytoplasmic sensors and triggering interferon production, can predispose patients to certain autoimmune diseases. Her laboratory discovered that the La protein, a prominent autoantigen in some patients with systemic autoimmune rheumatic disease, is a chaperone that stabilizes newly made RNAs from degradation and assists their folding, maturation and assembly with protein partners. They also identified the first La-related proteins (LARPs), members of an ancient protein superfamily that share a motif with the La protein. Their studies of another human autoantigen, the Ro60 protein, revealed that it is a key molecular component of a surveillance pathway that recognizes misfolded and otherwise defective RNAs for degradation. Ro60 function is regulated by noncoding RNAs called Y RNAs, and tethering of a bacterial Ro60 protein to a nuclease by Y RNA forms an RNP machine specialized for degrading structured RNA. In collaboration with Martin Kriegel, they provided evidence that bacterial Ro60 RNPs may act through molecular mimicry to trigger autoantibody formation in susceptible patients. The laboratory’s current goals are to uncover additional roles for Ro60 and Y RNAs in mammalian cells and bacteria, and to determine how these and other surveillance pathways contribute to normal cell physiology and prevent disease.