Regulatory role of small nucleolar RNAs in human diseases

Abstract

Small nucleolar RNAs (snoRNAs) are appreciable players in gene expression regulation in human cells. The canonical function of box C/D and box H/ACA snoRNAs is posttranscriptional modification of ribosomal RNAs (rRNAs), namely, 2'-O-methylation and pseudouridylation, respectively. A series of independent studies demonstrated that snoRNAs, as well as other noncoding RNAs, serve as the source of various short regulatory RNAs. Some snoRNAs and their fragments can also participate in the regulation of alternative splicing and posttranscriptional modification of mRNA. Alterations in snoRNA expression in human cells can affect numerous vital cellular processes. SnoRNA level in human cells, blood serum, and plasma presents a promising target for diagnostics and treatment of human pathologies. Here we discuss the relation between snoRNAs and oncological, neurodegenerative, and viral diseases and also describe changes in snoRNA level in response to artificial stress and some drugs.

Figure 1

(a) Box C/D snoRNAs share two conserved elements: boxes С (PuUGAUGA) and D (CUGA) located at the 5′- and 3′-termini of the RNA molecule, respectively. Often, box C/D snoRNAs also have an additional copy of internally located C′ or D′ boxes. A complex of box C/D snoRNA with nucleolar proteins Nop1p (fibrillarin), Nop56p, Nop58p, and Snu13p (15.5 kDa) catalyzes site-specific 2′-O-methylation of the nucleotide in target RNA. S-Adenosylmethionine (SAM) serves as the donor of the methyl group and is converted to S-adenosylhomocysteine (SAH). (b) Box H/ACA snoRNAs have “hairpin-hinge-hairpin-tail” structure with boxes H (ANANNA) and ACA located within the single-stranded (hinge) and 3′-terminus (tail) regions, respectively. Pseudouridylation complex includes dyskerin (the pseudouridine synthase), GAR1, NHP2, and NOP10 proteins. Box H/ACA snoRNP catalyzes site-specific isomerization of uridine (U) to pseudouridine (Ψ) in target RNA. ∗SnoRNA with target RNA in square brackets designates snoRNP enzyme-substrate complex.