Work in the Parker lab focuses on understanding the expression, location, and function of eukaryotic RNAs and their connection to human disease.
One focus of work is to understand RNP granules, which are large assemblies of RNA and protein in eukaryotic cells. We discovered that RNP granules are formed, at least in part, by promiscuous intermolecular RNA-RNA interactions, which suggests that RNP granules are analogous to protein aggregates. Consistent with this view, we discovered cells contain abundant RNA chaperones that limit promiscuous RNA interactions and allow RNAs to maintain their function. Current areas of work are to understand the breadth of the 鈥淩NA Chaperone Network鈥� and how defects in this network lead to neurological diseases.
A second focus of the lab is to understand how tau protein, which is an RNA binding protein, forms fibrillar protein aggregates and is toxic to neurons. This is important since aggregation of tau protein is responsible for ~75% of dementia caused by neurodegeneration. We have discovered that tau aggregates also contain RNA and preferentially grow off the surface of distinct RNP granules in the nucleus or cytoplasm. Current areas of work are to understand the biochemical interactions that promote tau fiber growth in cells, how those can be prevented, and how the interaction of tau with RNA affects neuronal health.
Additional work in the lab is focused on how the addition, and removal, of short oligo(A) tails to non-coding RNAs regulates their degradation rate. In this system, the addition of oligo(A) tails recruits processive 3鈥� exonucleases that degrade the non-coding RNA. In contrast, specific 鈥渄e-tailing鈥� enzymes can remove the oligo(A) tail and thereby protect the RNA from degradation. Strikingly, mutations in the three enzymes that remove the oligo(A) tails led to specific human diseases, which can be rescued in the laboratory by inhibiting the tail addition enzymes. Current work in this area is to understand the range of RNAs regulated by this pathway and how our understanding can be utilized to develop new disease treatments.
