Epigenetic control of gene expression is a critical component of transcriptional regulation. Remarkably, the deposition of epigenetic modifications is often guided by noncoding RNAs. Although noncoding RNAs have been most often implicated in posttranscriptional gene silencing, these molecules are now emerging as critical regulators of gene expression and genomic stability at the transcriptional level. Here, we review recent efforts to understand the mechanisms by which RNA controls the expression or content of DNA. We discuss the role of both small RNAs and long noncoding RNAs in directing chromatin changes through histone modifications and DNA methylation. Furthermore, we highlight the function of RNA in mediating DNA cleavage during genome rearrangements and pathogen defense. In understanding the mechanisms of RNA control over DNA, the power of RNA may one day be harnessed to impact gene expression in a therapeutic setting.
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