Non‐coding RNAs; epigenetic regulators of gene transcription in human cells

Abstract

Recent observations have demonstrated that exogenously introduced small antisense RNAs (asRNAs) can transcriptionally modulate gene expression in human cells. The mechanism involved in small asRNA directed transcriptional gene silencing (TGS) appears to involve DNA methyltransferase 3a (DNMT3a). However, an endogenous RNA trigger directing epigenetic regulatory proteins to targeted genomic loci in human cells has remained unknown. We present evidence here suggesting that long non‐coding asRNAs function in human cells as effector molecules driving TGS. These asRNAs, in some cases emanating from pseudogenes, function to guide epigenetic remodeling complexes consisting of Enhancer of Zeste (Ezh2) and DNMT3a to target loci. When these regulatory asRNAs are degraded using RNAi the result can be a concomitant activation of their protein‐coding counter part. Importantly, this RNA based transcriptional regulatory mechanism can be taken advantage of to either transcriptionally silence a genes expression in a long‐term manner or activate a genes transcription by the targeted degradation of the regulatory long antisense non‐coding RNAs.