Coordinated Expression of Retained Introns and Poison Exons in Renal Cell Carcinoma

Coordinated intron retention and poison exon inclusion define a subset of kidney tumors by introducing premature stop codons that typically trigger nonsense-mediated decay (NMD). In this study we investigate how mTOR activity modulates these NMD targets, revealing that mTOR inhibition increases the expression of transcripts bearing retained introns and poison exons in certain patient-derived tumors. Our findings show that tumors with low NMD and mTOR activities are more aggressive and have worse outcomes yet display pronounced immune infiltration, highlighting a potential role for these RNA isoforms in shaping tumor progression and immune responses. Overall design: A498 and A704 cells were treated with either DMSO, mTORi, SMG1i, or PladB, for 24 hours