c-Myc promoter-associated RNA (c-Myc pRNA)

c-Myc promoter-associated RNA (pRNA) is a non-coding RNA transcript that originates from the promoter region of the c-Myc (MYC) gene, typically initiated upstream of and overlapping the transcription start site [3, 7]. It functions as a key regulatory element in the transcriptional control of c-Myc, a potent oncogene involved in cell proliferation, differentiation, and apoptosis [1, 2]. The pRNA acts as a molecular scaffold that can be targeted by small interfering RNAs (siRNAs) to induce RNA-directed transcriptional interference (RdTI) [3, 6]. In this process, the siRNA binds to the pRNA and recruits Argonaute 2 (Ago2), which subsequently blocks the assembly of the transcription pre-initiation complex (PIC) at the c-Myc promoter, leading to robust gene silencing [3, 7]. As a therapeutic target, c-Myc pRNA is particularly significant because the c-Myc protein itself is notoriously difficult to target with traditional small molecules due to its lack of a defined binding pocket [1, 4]. Experimental promoter-targeted siRNAs, such as myc13, have shown efficacy in reducing c-Myc expression, resulting in growth arrest and the induction of a senescence-like phenotype in cancer cells, including prostate cancer models, while showing minimal toxicity to normal cells [3, 7]. This approach represents a promising strategy for treating c-Myc-driven malignancies by intervening at the level of transcriptional initiation rather than protein activity [3, 6].

Other names

MYC promoter-associated RNApRNAc-myc pRNAnoncoding promoter-associated RNAMYC-pRNA

RNA-directed transcriptional interference (RdTI) where small interfering RNAs (siRNAs) bind to the pRNA and recruit Argonaute 2 (Ago2) to the promoter, physically blocking the assembly of the transcription pre-initiation complex (PIC) and silencing gene expression.