Transcription factors (TFs) are proteins that regulate the gene expression programs and the identity of each cell by encountering numerous binding partners in the nucleus to turn transcription on or off. They bind regulatory elements of DNA such as promoters and enhancers via their DNA binding domains, and interact with various proteins via their effector domains such as coactivators or repressors. However, our lab and others have discovered that TFs engage in a third type of interaction, which is binding RNA.
In collaboration with the Batey Lab at CU, we have characterized the non-canonical RNA binding domains of the TFs Sox2, glucocorticoid receptor, estrogen receptor alpha, and GATA1. WWe found that all of these TFs, while bind DNA with sequence specifcity, interact with RNA via structural specifcity with strong preference for a hairpin. Importantly, these TFs bind RNA via their DBDs (in the case of Sox2) or via residues just downstream of their DBDs in a flexible hinge region (in the cases of GR, ERa, and GATA1).
We are continuing to investigate the in vivo roles of RNA binding by TFs by using separation of funciton mutagenesis to study transcriptional output, chromatin occupancy, and genomic architecture of cells lacking RNA binding capacities.