Using high-throughput sequencing to study RNA secondary structure and RNA-protein interactions globally

We have pioneered the development of high-throughput, sequencing-based approaches to simultaneously study RNA secondary structure and RNA-protein interactions on a global scale. To do this, we have married classical nuclease-based structure mapping techniques with high-throughput sequencing technology to interrogate the protein binding profile and pairing status of all nucleotides in the RNA molecules of eukaryotic organisms. We believe that the findings from these approaches highlight the importance of RNA-protein interactions and RNA secondary structure in eukaryotes and present an approach that should be widely applicable for the analysis of these key features in any and all organisms.

We are also using these approaches to identify all small (sm)RNA-producing substrates of RNA-DEPENDENT RNA POLYMERASEs (RDRs). More specifically, we use the combination of transcriptome-wide double-stranded (dsRNA) and small RNA sequencing to interrogate the substrates of this class of enzymes in eukaryotes. We are currently characterizing the RDRs of Arabidopsis thaliana.

Mechanisms and regulation of the transcriptome by RNA covalent modifications

We also make use of genomic, bioinformatic, and systems biology approaches with molecular genetic and biochemical techniques to identify and characterize the post-transcriptional regulatory effects of RNA covalent modifications in eukaryotic transcriptomes.