RNA accessibility sequencing reveals transcriptome-wide RBP binding and RNA structure

Researchers have developed a new technique called RAD-seq, or RNA Accessibility via Deamination sequencing, which can measure the accessibility of RNA to protein binding in living organisms. This method involves chemically modifying adenosine nucleotides that are exposed to their molecular environment, taking into account various factors such as base pairing, RNA folding, and the presence of RNA-binding proteins.

The resulting data from RAD-seq experiments align with known structural patterns, provide detailed maps of protein binding sites on RNA, and show how RNA modifications and environmental stressors affect RNA accessibility. By combining RAD-seq data with information on RNA binding motifs, scientists were able to detect the presence of a protein called TRA2A, which helps recruit another methyltransferase to RNA, following the reduction of a protein called EIF4A3.

This suggests a possible pathway for how changes in RNA accessibility can influence the binding and modification of RNA. Furthermore, the researchers created a statistical model that uses RAD-seq data along with known binding patterns to create comprehensive maps of how multiple proteins interact with RNA, using just one RAD-seq experiment.

This approach opens up the possibility of simultaneously studying the three-dimensional structure of RNA and the occupancy of various proteins, with the added insight that the chemical modification of RNA itself can be a regulatory factor.