Analysis of gene expression in C. elegans. For the approximately 650 genes of this panel, relative levels of steady-state mRNA contained in wild type (red probe) are compared to those of a smg(-) mutant (green probe). (D. Markwardt and P. Anderson)
Our focus group examines all aspects of RNA, using interdisciplinary approaches. RNAs are a fascinating group of molecules, and raise a collection of fundamental and unsolved problems. RNA structure and assembly. RNAs possess idiosyncratic and highly organized structures. RNAs can be catalytic, with dynamic structures that must assemble in a specific fashion, yet change in conformation in specific ways. How do RNAs fold, and how do they change in conformation? How do they catalyze reactions?
RNAs are at the molecular heart of basic cellular machines, like the ribosome and spliceosome. How do those machines work, and how are they put together? RNA maturation. Mature RNAs are produced in cells through a complex array of steps, each one of which can be regulated. For eukaryotic mRNAs, these steps include transport between the nucleus and cytoplasm, splicing, and polyadenylation. How are those steps executed, and how are they linked to one another?
The regulation of mRNAs is vital in virtually all aspects of biology, including development, cell biology, cancer biology, and virology. Regulation of the translation, stability and localization of mRNAs are critical: they can determine when, where, and how much protein is produced. How is that regulation accomplished? RNA regulation in human health and disease. The dysfunction of mRNA based controls underlies many pathological conditions. How does it go awry, and can it be corrected?
Many events in an mRNA's life are governed by the specific interaction of RNAs with proteins. What general principles underlie these interactions and how are they regulated in the cell? To approach these questions, our interest group uses a wide range of approaches, including genetics, cell and developmental biology, molecular biology, biochemistry and structural analysis. We exploit many organisms, including yeast, C. elegans, Xenopus and mammalian cells, as well as RNA viruses.