Non-MYC mRNAs with seed-region complementarity

Non-MYC mRNAs with seed-region complementarity refers to a broad class of messenger RNAs that are targeted by small RNAs (siRNAs or shRNAs) through a mechanism involving partial sequence matches, specifically in the 6-8 nucleotide seed region (Gao et al., 2018). This interaction is the basis for Death Induced by Survival gene Elimination (DISE), a process where the simultaneous silencing of multiple genes essential for cell survival triggers extensive apoptosis in cancer cells (Putzbach et al., 2017). While this effect was historically viewed as an off-target complication in MYC-directed RNAi therapies, it has emerged as a potential therapeutic strategy due to its ability to kill cancer cells regardless of their genetic driver or resistance profile (Peter, 2017). The mechanism involves the RNA-induced silencing complex (RISC) binding to the 3' untranslated regions (UTRs) of these survival-critical mRNAs, leading to their degradation or translational inhibition (Hadji et al., 2014). However, the lack of specificity inherent in seed-based targeting poses significant safety challenges, as it can lead to non-selective cell death in healthy tissues if not precisely delivered (Gao et al., 2018).

Other names

DISE targetsSurvival gene transcripts6-mer seed-matched mRNAsOff-target survival genesDeath Induced by Survival gene Elimination targets

Seed-region dependent RNA interference (RNAi) leading to multi-gene silencing and Death Induced by Survival gene Elimination (DISE)