Non-OGG1 messenger RNAs with seed-region complementarity

Non-OGG1 messenger RNAs with seed-region complementarity refers to a collective group of transcripts that are unintentionally targeted by RNA interference (RNAi) agents, such as siRNAs or shRNAs, originally designed to silence the 8-Oxoguanine glycosylase (OGG1) gene. This phenomenon occurs because the seed region (nucleotides 2-8) of the siRNA can bind to complementary sequences in the 3' untranslated regions (UTRs) of numerous other mRNAs, leading to their degradation or translational repression (Putzbach et al., 2017). In the context of OGG1 research, this has been identified as a significant source of experimental artifact, where observed cell death is often not due to OGG1 inhibition but rather to the simultaneous silencing of multiple essential survival genes. This mechanism is a key component of Death Induced by Survival gene Elimination (DISE), a form of off-target toxicity that poses a challenge in the development of RNAi-based therapeutics and the validation of OGG1 as a drug target (Peter et al., 2019). Consequently, these mRNAs are not considered valid therapeutic targets but are instead critical factors to account for in safety assessments and experimental design. Understanding these interactions is vital for distinguishing between true target-dependent effects and sequence-specific off-target toxicity (Hadji et al., 2014).

Other names

Off-target mRNAsSeed-matched transcriptsDISE-associated mRNAsRNAi off-targetsToxic seed transcripts

RNA interference (RNAi) mediated silencing via seed-region complementarity in the 3' untranslated region (UTR) of non-target transcripts (Putzbach et al., 2017).