The mechanism of RNA directed transcriptional gene silencing in human cells
The promoter-associated RNA model of RNA mediated transcriptional gene silencing proposes that a variant species of mRNA, a promoter associated mRNA, essentially an mRNA containing an extended 5´ UTR, is recognized by the antisense strand of siRNAs or possibly endogenous antisense RNAs during the act of transcription of the small RNA targeted promoter (A).
The antisense strand of the siRNA might then guide a putative transcriptional silencing complex (composed of DNMT3A, Ago-1, HDAC-1, and possibly Ezh2) to the targeted promoter where silent-state histone modifications result in the initial gene-silencing event (B).
The prolonged targeting of the promoter may result in heterchromatization and/or DNA methylation of the small RNA targeted loci (C).