The Parker lab addresses the regulation of RNA molecules, how that impacts normal physiology of eukaryotic cells, and how aberrant RNA regulation contributes to human disease.  The major focuses in the lab are in three areas:

Regulation of RNA degradation by tailing and de-tailing

            It is now clear the degradation of a number of RNA species including telomerase RNA, miRNAs, and other ncRNAs are regulated by the addition of oligo(U) or oligo(A) tails, that "tag" the RNA for degradation and recruit processive 3' to 5' exonucleases.  Moreover, a family of poly(A) specific deadenylases can remove oligo(A) tails promoting RNA decay and thereby protect the RNAs from degradation.  This process of tailing and de-tailing can be considered analogous to the ubiquination, and de-ubiquination, of proteins for degradation by the proteasome.  Projects in this area include understanding the range of RNAs regulated by these pathways, and how specificity is controlled both for tailing and de-tailing enzymes.

Understanding the "RNA Chaperone" network

            In our studies of RNP granules, we have discovered that promiscuous intermolecular RNA-RNA interactions can promote the formation of RNP granules.  Moreover, cells must modulate such interactions to allow the proper function of RNAs and to prevent aberrant RNA granule formation.  We study the mechanisms that regulate intermolecular RNA-RNA interactions.  This includes the study of abundant "RNA chaperones" that function similarly to protein chaperones to prevent aberrant RNA "aggregation".  We also investigate how cells have taken advantage of this fundamental propensity of RNA molecules to evolve novel regulatory mechanisms.

Understanding the connections of RNA and Tau

            Another project in the lab is to understand the function of the tau protein in RNA metabolism, and how RNP granules interact with tau aggregates. These are important issues for two reasons. First, the tau protein forms intracellular aggregates consisting of fibrillar forms of tau in multiple neurological diseases and those assemblies, particularly at oligomeric scales, contribute to the neurodegenerative process. Given this, determining how tau aggregation occurs within the cell, and how it alters cell physiology, is critical for understanding neurodegeneration. Second, it is important to understand the normal function of the tau protein. Tau is generally thought to bind to, and regulate, microtubules. However, tau binds RNA, interacts with RNA-binding proteins, and may have unknown roles in RNA metabolism. An understanding of the normal function(s) of tau will inform the fundamental biology of this critical protein and may provide insight into the causes and consequences of tau aggregation.