#25 · Structural bio & protein design

Predicted YTHDC1 docking to ADAR1 Zα links m6A pre-mRNA marks to dsRNA editing

The dominant thread is structure-guided computational design applied to RNA-centric systems. A preprint reports RFdiffusion/ProteinMPNN-guided screening with AlphaFold3 and molecular dynamics, predicting that the YTHDC1 glutamate-rich domain docks to the ADAR1 Zα domain to form a dsRNA-bridged ternary complex. This would connect N6-methyladenosine on pre-mRNAs to dsRNA editing. A Science paper uses structure-guided inverse folding and evolutionary constraints to design active divergent TnpB nucleases (SynTnpBs) for genome editing. SNIPSNP, a published bioinformatics pipeline, designs CRISPR HDR reagents by selecting blocking silent variants and guides that reduce Cas9 re-cleavage. Only the first item addresses RNA modification directly; the other two share the design framing rather than the RNA-modification biology. What is new is the proposed YTHDC1-ADAR1 Zα bridge, which is a computationally predicted interaction.