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.

Along with SNORD115 and SNORD116, a number of other human snoRNAs can generate smaller fragments, as it has been demonstrated by high-throughput sequencing and RNase protection experiments [21] [22] [23] . Short fragments derived from box C/D snoRNA SNORD88C (HBII-180C) hold complementarity to fibroblast growth receptor-3 (FGFR-3) pre-mRNA. Being expressed from artificial "snoMEN" vector, SNORD88C (HBII-180C) is capable of suppressing target gene mRNA and protein level in a sequence-dependent manner through base pairing with pre-mRNA regulatory elements [24, 25] . Bioinformatic analysis showed that about a half of all box C/D RNAs are processed into small molecules that are conserved among multiple cell lines [26] . Box H/ACA snoRNAs are usually processed into 20-24 nt fragments, while box C/D-derived RNAs are ∼17-19 or >24 nt long. These fragments are termed snoRNA-derived RNAs (sdRNAs) and considered to be a novel class of regulatory RNAs. Most of sdRNAs preserve conserved C/D or H/ACA box pairs [21, 27, 28] . Moreover, several sdRNAs were found to interact with Ago family proteins, the key components of RISC complexes [29, 30] . It was shown that a number of box C/D RNA-derived fragments can exhibit miRNA activity [28] . However, the mechanism underlying the biogenesis of such snoRNA derivatives that resemble microRNAs still remains unknown. It has been shown that processing of box C/D RNAs into sdRNAs was Dicer-independent, while production of box H/ACA-derived sdRNAs required Dicer [29, 31] . Thus, snoRNAs can serve as a source of short regulatory RNA species involved in the control of processing and translation of various mRNAs.