Regulatory Role of Small Nucleolar RNAs in Human Diseases

Stepanov, Grigory A.; Filippova, Julia A.; Komissarov, Andrey B.; Kuligina, Elena V.; Richter, Vladimir A.; Semenov, Dmitry V.

The first evidence of the existence of snoRNA encoded in viral genomes was obtained from the studies on herpesviruses. A box C/D RNA termed as v-snoRNA1 (viral small nucleolar RNA1) has been found in B lymphocytes infected with Epstein-Barr virus (EBV) [81] . This RNA was 65 nt long and encoded within the viral genome. Despite the fact that the viral box C/D RNA has C/D and C /D pairs of boxes and contains short regions (9-11 nt) complementary to human 18S and 28S rRNAs, the further analysis did not reveal 2 -O-methylation of potential rRNA target nucleotides in infected cells [81] . Apart from the full-length box C/D RNA, a 24-nt RNA that represents a 3 -terminal fragment (41st to 64th nt) of the viral box C/D RNA, v-snoRNA1 24pp , was found in cells infected with EBV. In EBV genome v-snoRNA1 is encoded in the antisense direction to 3 -UTR of DNA polymerase gene (BALF5). It has been shown that v-snoRNA1 24pp is able to interact with BALF5 mRNA and induce specific hydrolysis of target mRNA in the region of complementarity. The levels of the viral box C/D RNA and its shortened form increase 30-fold in cells during the lytic phase of infection. It has also been established that the level of BALF5 mRNA in infected cells is controlled by the viral microRNA miR-BART2 during transition from latent to lytic phase [82] . Therefore, it is reasonable to assume that activation of viral box C/D RNA expression and its processing to short regulatory form enables a more rapid decrease in a target mRNA level. Bioinformatic analysis has demonstrated that a cognate box C/D RNA is encoded within the genome of another -herpesvirus, rhesus monkey Lymphocryptovirus [81] . The presence of box C/D RNA in viral genome indicates that viruses are able to utilize snoRNAdependent mechanisms for the regulation of their life cycle.