Specific silencing of leukemic oncogenes using RNA-interference approach

Abstract

Non-coding rNAs are widespread class of cell rNAs. they participate in many important processes in cells-signaling, posttranscriptional silencing, protein biosynthesis, splicing, maintenance of genome stability, telomere lengthening, X-inactivation. Nevertheless, activity of these rNAs is not restricted to posttranscriptional sphere, but cover also processes that change or maintain the epigenetic information. Non-coding rNAs can directly bind to the DNA targets and cause their repression through recruitment of DNA methyltransferases as well as chromatin modifying enzymes. Such events constitute molecular mechanism of the rNA-dependent DNA methylation. It is possible, that the rNA-DNA interaction is universal mechanism triggering DNA methylation de novo. Allelic exclusion can be also based on described mechanism. this phenomenon takes place, when non-coding rNA, which precursor is transcribed from one allele, triggers DNA methylation in all other alleles present in the cell. Note, that mirNA-mediated transcriptional silencing resembles allelic exclusion, because both mirNA gene and genes, which can be targeted by this mirNA, contain elements with the same sequences. It can be assumed that rNA-dependent DNA methylation and allelic exclusion originated with the purpose of counteracting the activity of mobile genetic elements. Probably, thinning and deregulation of the cellular non-coding rNA pattern allows reactivation of silent mobile genetic elements resulting in genome instability that leads to ageing and carcinogenesis. In the course of X-inactivation, DNA methylation and subsequent hete rochromatinization of X chromosome can be triggered by direct hybridization of 5′-end of large non-coding rNA Xist with DNA targets in remote regions of the X chromosome.