Epigenetics of Ribosomal RNA Genes.

This review is focused on biology of genes encoding ribosomal RNA (rRNA) in mammals. rRNA is a structural component of the most abundant cellular molecule, the ribosome. There are many copies of rRNA genes per genome that are under tight transcriptional control by epigenetic mechanisms serving to meet cellular needs in protein synthesis. Curiously, only a fraction of rRNA genes is used even in the fast-growing cells, raising a question why unused copies of these genes have not been lost during evolution. Two plausible explanations are discussed. First, there is evidence that besides their direct function in production of rRNA, ribosomal RNA genes are involved in regulation of many other genes in the nucleus by forming either temporary or persistent complexes with these genes. Second, it seems that rRNA genes also play a role in the maintenance of genome stability, where lower copy number of rRNA genes destabilizes the genome. These "additional" functions of rRNA genes make them recurrent candidate drivers of chronic human diseases and aging. Experimental support for the involvement of these genes in human diseases and potential mechanisms are also discussed.