A research team led by Rice University’s Yang Gao has uncovered new insights into the molecular mechanisms of ADAR1, a protein that regulates ribonucleic acid (RNA) induced immune responses. Their findings, published in Molecular Cell March 17, could open new pathways for treating autoimmune diseases and enhancing cancer immunotherapy.

ADAR1 converts adenosine to inosine in double-stranded RNA, a process essential for preventing unwarranted immune responses, yet the molecular basis of this editing had remained unclear. Through detailed biochemical profiling and structural analysis, researchers found that ADAR1’s editing activity depends on RNA sequence, duplex length and mismatches near the editing site. High-resolution structures of ADAR1 bound to RNA reveal its mechanisms for RNA binding, substrate selection and dimerization.

“Our study provides a comprehensive understanding of how ADAR1 recognizes and processes RNA,” said Gao, assistant professor of biosciences and a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar. “These insights pave the way for novel therapeutic strategies targeting ADAR1-related diseases.”