Biology and applications of small nucleolar RNAs

Abstract

Small nucleolar RNAs (snoRNAs) constitute a group of non-coding RNAs principally involved in posttranscriptional modification of ubiquitously expressed ribosomal and small nuclear RNAs. However, a number of tissue-specific snoRNAs have recently been identified that apparently do not target conventional substrates and are presumed to guide processing of primary transcripts of protein-coding genes, potentially expanding the diapason of regulatory RNAs that control translation of mRNA to proteins. Here, we review biogenesis of snoRNAs and redefine their function in light of recent exciting discoveries. We also discuss the potential of recombinant snoRNAs to be used in modulation of gene expression.

Fig. 1

Structural features of the modification guide snoRNA families and types of posttranscriptional modifications they promote. Schematic secondary structures of a box C/D snoRNAs and b box H/ACA snoRNA are shown on top. Substrate RNA is depicted in gray. Sites targeted for nucleotide modification are indicated with block arrows. Me stands for 2′-O-methyl group introduced onto the ribose ring (c) and ψ represents pseudouridine (d)

Fig. 2

Model describing SNORD115 processing and the action of resulting psnoRNAs (adapted from [2]). a The snoRNA-rich imprinted locus 15q11-q13 contains 47 copies of SNORD115 (thick line; a single copy is shown for simplicity) located in introns between non-coding exons (open boxes). The snoRNA is characterized by stem-forming sequences (arrowheads), box C, box D, and an antisense element (AE). b This unit generates the canonical SNORD115, which localizes to nucleolus and Cajal bodies (possibly serving as storage sites), as well as a number of shorter nucleoplasmic RNAs, called processed snoRNAs (psnoRNAs), which associate with heterogenous nuclear ribonucleoproteins (hnRNPs). c psnoRNAs can change splice-site selection by binding to complementary sequences. psnoRNA either displace regulatory proteins (open circle) from pre-mRNA tagets or act as guides for hnRNPs (black circles), functioning as exon recognition complexes