Figure 3. Perturbation approaches for the functional characterization of a candidate lncRNA locus.

Whereas RNA-centered methods (RNAi, LNA) specifically perturb the RNA molecule without affecting the DNA locus, genomic deletions are powerful loss-of function approaches, but can not differentiate between DNA-mediated and RNA-mediated functions of a given gene. CRISPRi is a technique where a nuclease-dead Cas9 protein is coupled to a transcriptional repressor and thereby mediates gene silencing.