MYC’s RNA Trick Drives Immune Evasion in Pancreatic Cancer

Researchers identify a mechanism where the MYC protein shifts from DNA to nascent RNA under stress, using an RNA-binding region (RBRIII) to promote multimerization and recruit the nuclear exosome to degrade RNA at R-loops, thereby suppressing innate immune signaling (via TLR3 and TBK1) in pancreatic cancer. Mutating the RNA-binding region prevents this immune suppression and causes tumor regression in immunocompetent mice, suggesting therapies that block MYC’s RNA-binding function could expose tumors to immune attack while preserving MYC’s transcriptional activity.