Exploring the world of dual RNA and DNA binding proteins in human embryonic stem cells
We are currently developing a proteomic-based methodology to uncover the repertoire of dual binding DNA and RNA binding proteins (DRBPs) in human embryonic stem cells (hESCs), motivated by recent evidence demonstrating the ability of transcription factors to bind diverse types of RNA. Strikingly, this contrasts with the common view that proteins that bind DNA are functionally distinct from proteins that bind RNA. As a proof of concept, we experimentally determined the mRNA-bound proteome of hESCs, identifying over 800 high-confidence RNA-binding proteins, including 175 candidate DRBPs. Our preliminary results suggest that some DRBPs may shape the stem cell state via fine tuning of gene expression regulation.
A pie chart summarizing the proteomic results of the RNA interactome capture in hESCs. As shown, ~23% of the proteins captures as RNA binding proteins have been previously shown to bind DNA in other system, these proteins are defined as DRBPs. Consistently, a detailed analysis of the proteins found to be differentially expressed in hESCs relative to other human tissues confirmed their involvement in both transcriptional and post-transcriptional processes. In addition, we found that a significant number of the DRBPs were differentially expressed when differentiating hESCs to embryoid bodies.