Abstract: Observations over the past nine years have determined that in human cells non-coding RNAs (ncRNAs) transcriptionally modulate gene expression and epigenetic states. One mechanism involved in antisense ncRNA directed transcriptional gene silencing (TGS) appears to involve DNA methyltransferase 3a (DNMT3a) and Ehancer of Zeste 2 (EZH2). Some of the ncRNAs found to operate in this pathway have been shown to exhibit bimodal functionalities, whereby they can function in both a nuclear and cytoplasmic context via higher ordered complex RNA:RNA interactions. We present evidence here suggesting that HIV is also under this form of RNA directed epigenetic regulation. Collectively, the data presented here offer subtle insights into the fabric of ncRNA based regulation in human cells while simultaneously suggesting that a mechanism of action can be taken advantage of to either transcriptionally silence or activate a gene for therapeutically relevant outcomes.
Grant acknowledgments NIAID PO1 AI099783-01 and NCI of the NIH CA151574 and R01 CA153124.