TRUE Gene Silencing

TRUE gene silencing is an RNA-mediated gene expression control technology and is termed after tRNase Z(L)-utilizing efficacious gene silencing. In this review, I overview the potentiality of small guide RNA (sgRNA) for TRUE gene silencing as novel therapeutics. First, I describe the physiology of tRNase Z(L) and cellular small RNA, and then sgRNA and TRUE gene silencing. An endoribonuclease, tRNase Z(L), which can efficiently remove a 3′ trailer from pre-tRNA, is thought to play the role in tRNA maturation in the nucleus and mitochondria. There exist various small RNAs including miRNA and fragments from tRNA and rRNA, which can function as sgRNA, in living cells, and human cells appear to be harnessing cytosolic tRNase Z(L) for gene regulation together with these small RNAs. By utilizing the property of tRNase Z(L) to recognize and cleave micro-pre-tRNA, a pre-tRNA-like or micro-pre-tRNA-like complex, as well as pre-tRNA, tRNase Z(L) can be made to cleave any target RNA at any desired site under the direction of an artificial sgRNA that binds a target RNA and forms the pre-tRNA-like or micro-pre-tRNA-like complex. This general RNA cleavage method underlies TRUE gene silencing. Various examples of the application of TRUE gene silencing are reviewed including the application to several human cancer cells in order to induce apoptosis. Lastly, I discuss the potentiality of sgRNA as novel therapeutics for multiple myeloma.