Transcription factor-associated regulatory RNA (Tf-RNA)

Transcription factor-associated regulatory RNAs, primarily long non-coding RNAs (lncRNAs), are a class of molecules that modulate the activity, stability, or localization of high-value transcription factors (TFs) such as MYC, p53, and the Androgen Receptor. These RNAs can act as molecular scaffolds to facilitate the assembly of transcriptional complexes, as decoys to sequester TFs away from their target DNA, or as guides to recruit TFs to specific genomic loci. In many diseases, particularly cancer, these regulatory RNAs are dysregulated, leading to the aberrant activation of oncogenic TFs or the silencing of tumor suppressors. Targeting the interaction between these RNAs and their associated TFs represents a novel therapeutic strategy, with companies like NextRNA Therapeutics and Haya Therapeutics developing small molecules and antisense oligonucleotides to disrupt these pathological complexes. This approach offers the potential to drug the undruggable by indirectly modulating TFs that have traditionally been difficult to target with conventional small molecules.

Other names

Transcription factor-regulatory RNAlncRNA-TF complexRegulatory non-coding RNATf-RNATranscription factor-associated RNA

Disruption of lncRNA-protein interaction, Targeted degradation of regulatory RNA, Inhibition of lncRNA-mediated recruitment of transcription factors