DNA-guided Photoactivatable Probe-based Chemical Proteomics Reveals the Reader Protein

We report a DNA templated chemistry and photo-crosslinking based method to detect the readers of mRNA modification. By use of N6-methyladenosine (m6A), we illustrated that this method can be successfully utilized for labelling and enriching the readers of mRNA modification, as well as for the discovery of new partners. Thus we applied this strategy to a new modification 2'-O-methyladenosine. As a result, DDX1 was identified and verified as a potential reader by in vitro and in vivo experiments. Our study therefore provides a powerful chemical proteomics tool for identifying the readers of mRNA modification and reveals the underlying function of mRNA modification.