Small RNA-mediated chromatin modification and transcriptional gene silencing

Small RNAs, such as short-interfering RNAs (siRNAs) and microRNAs (miRNAs), regulate gene expression in a sequence-dependent manner in animals and plants. These small RNAs are generated from long double-stranded (ds) RNAs or pre-miRNAs by the ribonuclease Dicer and become incorporated into RNA interference (RNAi)-induced silencing complexes (RISCs) or miRNA ribonucleoprotein complexes (miRNPs). These complexes have the ability to cleave target mRNAs with perfect base-pairing and inhibit the translation of target mRNAs with partial base-pairing. In addition, small RNAs can also act on the chromosomes in the nucleus. In this process, it is known that siRNAs targeted to CpG islands within promoters can induce RNA-directed DNA methylation and play a role in heterochromatic gene silencing. Thus, small RNAs can regulate gene expression at both the transcriptional and post-transcriptional levels. In this review, we focus on small RNA-mediated transcriptional gene silencing and on its role and potential therapeutic applications in chromosome maintenance and gene regulation, including epigenetic regulation.