fig2

Figure 2. Schematic illustration of strategies used to target lncRNA. (A) siRNAs: siRNAs bind to lncRNA and recruit RISC, resulting in degradation of the lncRNA. (B) ASOs: ASOs bind to lncRNA and recruit RNaseH, resulting in degradation of the lncRNA and altered downstream protein expression. (C) CRISPR-Cas9: The inactive Cas9 domain is bound to a transcriptional activator domain or a transcriptional stop signal, so that when it binds to the complementary DNA that encodes the lncRNA gene, it results in either transcriptional activation at the promoter, or repression through blocking RNA polymerase, respectively. (D) Small molecules: the first small molecules designed for modulating lncRNA expression can be classified as interaction element blockers (IEBs) or structural element lockers (SELs). IEBs block the binding of lncRNA to its target, which in some cases can be used to increase expression levels of lncRNAs that would normally undergo nonsense-mediated decay due to their normal binding. SELs work by binding to lncRNAs and disrupting secondary (2°) structures which stabilise the lncRNA, thus resulting in destabilisation and reduced expression.