Identification of discrete classes of small nucleolar RNA featuring different ends and RNA binding protein dependency

Deschamps-Francoeur, Gabrielle; Garneau, Daniel; Dupuis-Sandoval, Fabien; Roy, Audrey; Frappier, Marie; Catala, Mathieu; Couture, Sonia; Barbe-Marcoux, Mélissa; Elela, Sherif Abou; Scott, Michelle S.

doi:10.1093/nar/gku664

Cited by 40 publications

(59 citation statements)

References 75 publications

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“…The RNA guides this enzymatic activity predominantly to rRNAs using one or two accessible snoRNA parts, the antisense boxes. However, about one-half of 267 human snoRNAs show no sequence complementarity toward other ncRNAs and thus, are orphan, suggesting additional functions (25,56). Genome-wide analysis of SNORD-rRNA interaction revealed additional basepairing regions and suggested an asymmetric binding of proteins to human SNORDs (57).…”

Section: Discussionmentioning

confidence: 99%

“…For example, changes in the expression of SNORD27, -30, -25, and -31 mark the progression of smoldering multiple myeloma (21), and SNORD50 deletions are associated with prostate and breast cancer (22)(23)(24). Genome-wide comparison of SNORD expression between cancer and normal cells showed the presence of two classes of SNORDs that differ in their terminal stems but are made from the same SNORD hosting intron (25).…”

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confidence: 99%

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Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing

Falaleeva

Pagès

Matuszek

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

171

152

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C/D box small nucleolar RNAs (SNORDs) are small noncoding RNAs, and their best-understood function is to target the methyltransferase fibrillarin to rRNA (for example, SNORD27 performs 2′-Omethylation of A27 in 18S rRNA). Unexpectedly, we found a subset of SNORDs, including SNORD27, in soluble nuclear extract made under native conditions, where fibrillarin was not detected, indicating that a fraction of the SNORD27 RNA likely forms a protein complex different from canonical snoRNAs found in the insoluble nuclear fraction. As part of this previously unidentified complex, SNORD27 regulates the alternative splicing of the transcription factor E2F7 pre-mRNA through direct RNA-RNA interaction without methylating the RNA, likely by competing with U1 small nuclear ribonucleoprotein (snRNP). Furthermore, knockdown of SNORD27 activates previously "silent" exons in several other genes through base complementarity across the entire SNORD27 sequence, not just the antisense boxes. Thus, some SNORDs likely function in both rRNA and pre-mRNA processing, which increases the repertoire of splicing regulators and links both processes.alternative splicing | gene regulation | snoRNAs | pre-mRNA processing S mall nucleolar RNAs (snoRNAs) are 60-to 300-nt-long noncoding RNAs that accumulate in the nucleolus. Based on conserved sequence elements, snoRNAs are classified as C/D box small nucleolar RNAs (SNORDs) or H/ACA box snoRNAs (SNORAs). SNORDs contain sequence elements termed C (RUGAUGA) and D (CUGA) boxes, usually present in duplicates (C′ and D′ boxes), and up to two antisense boxes that hybridize to the target RNA (1). In humans, SNORDs are usually derived from introns. After the splicing reaction, introns are excised as lariats, which are then opened by the debranching enzyme and subsequently degraded. Intronic SNORDs escape this degradation by forming a protein complex that consists of non-histone chromosome protein 2-like 1 (NHP2L1, 15.5K, SNU13), nucleolar protein 5A (NOP56), nucleolar protein 5 (NOP58), and fibrillarin (2-4). The SNORD protein complex forms through the entry of the snoRNA and fibrillarin to a complex containing NHP2L1, NOP58, and at least five assembly factors (5). The SNORD acts as a scaffold for the final protein complex formation and also controls recognition of other RNAs using the antisense boxes. The antisense boxes recognize sequences in rRNA, resulting in the fifth nucleotide upstream of the D or D′ box being 2′-O-methylated by fibrillarin (1). Structural studies indicate that the active form of SNORDs is dimeric (6).The conserved overall structure of SNORDs allows the identification of their putative target RNA binding sites. However, numerous SNORDs without obvious target RNAs have been identified (7-10) and are termed "orphan snoRNAs." Genome-wide deep sequencing experiments identified shorter but stable SNORD fragments that were found in all species tested, ranging from mammals to the protozoan Giardia lamblia (11) and EpsteinBarr virus (12). Fragments longer than 27 nt generated by SNORDs will ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing

Falaleeva

Pagès

Matuszek

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

171

152

View full text Add to dashboard Cite

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“…Almost all of the currently known 267 human SNORDs are located in introns, with the exception of SNORD3@ (@ indicating all four human SNORD3 genes, see Box 1 for SNORD nomenclature), SNORD8, SNORD13, and SNORD118 (U8) that are controlled by their own promoters [7, 8]. The intronic localization connects SNORD biogenesis with the pre-mRNA processing of their hosting genes.…”

Section: The Classic Picture Of Snornasmentioning

confidence: 99%

“…However, a target could be identified for only half of the known SNORDs. The remaining SNORDs were thus considered “orphan” [8, 30], suggesting that they might have other functions than 2′-O-methylation. The association of changes in SNORD expression with numerous diseases, where there were no obvious defects in ribosomal function, supports the concept that SNORDs mediate additional functions beyond rRNA methylation.…”

Section: Diseases Caused By Snorna Loss Indicate New Functionsmentioning

confidence: 99%

C/D‐box snoRNAs form methylating and non‐methylating ribonucleoprotein complexes: Old dogs show new tricks

et al. 2017

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C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non-coding RNAs that have been long known to perform 2′-O-methylation of rRNAs. However, approximately half of human SNORDs have no predictable rRNA targets, and numerous SNORDs have been associated with diseases that show no defects in rRNAs, among them Prader-Willi syndrome, Duplication 15q syndrome and cancer. This apparent discrepancy has been addressed by recent studies showing that SNORDs can act to regulate pre-mRNA alternative splicing, mRNA abundance, activate enzymes, and be processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent biochemical studies have shown that a given SNORD can form both methylating and non-methylating ribonucleoprotein complexes, providing an indication of the likely physical basis for such diverse new functions. Thus, SNORDs are more structurally and functionally diverse than previously thought, and their role in gene expression is under-appreciated. The action of SNORDs in non-methylating complexes can be substituted with oligonucleotides, allowing devising therapies for diseases like Prader-Willi syndrome.

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“…These motifs have the same consensus sequence as the C and D boxes, resp., but show a higher level of variation in both animals and plants. The assembly of box C/D snoRNPs involves the formation of a kink-turn (K-turn) motif [16, 17]. This involves the the alignment of the C and D boxes and the formation of a crucial non-canonical G:A pair across the asymmetric bulge [18–21].…”

Section: Introductionmentioning

confidence: 99%

Phylogenetic distribution of plant snoRNA families

et al. 2016

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BackgroundSmall nucleolar RNAs (snoRNAs) are one of the most ancient families amongst non-protein-coding RNAs. They are ubiquitous in Archaea and Eukarya but absent in bacteria. Their main function is to target chemical modifications of ribosomal RNAs. They fall into two classes, box C/D snoRNAs and box H/ACA snoRNAs, which are clearly distinguished by conserved sequence motifs and the type of chemical modification that they govern. Similarly to microRNAs, snoRNAs appear in distinct families of homologs that affect homologous targets. In animals, snoRNAs and their evolution have been studied in much detail. In plants, however, their evolution has attracted comparably little attention.ResultsIn order to chart the phylogenetic distribution of individual snoRNA families in plants, we applied a sophisticated approach for identifying homologs of known plant snoRNAs across the plant kingdom. In response to the relatively fast evolution of snoRNAs, information on conserved sequence boxes, target sequences, and secondary structure is combined to identify additional snoRNAs. We identified 296 families of snoRNAs in 24 species and traced their evolution throughout the plant kingdom. Many of the plant snoRNA families comprise paralogs. We also found that targets are well-conserved for most snoRNA families.ConclusionsThe sequence conservation of snoRNAs is sufficient to establish homologies between phyla. The degree of this conservation tapers off, however, between land plants and algae. Plant snoRNAs are frequently organized in highly conserved spatial clusters. As a resource for further investigations we provide carefully curated and annotated alignments for each snoRNA family under investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3301-2) contains supplementary material, which is available to authorized users.

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Identification of discrete classes of small nucleolar RNA featuring different ends and RNA binding protein dependency

Cited by 40 publications

References 75 publications

Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing

Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing

C/D‐box snoRNAs form methylating and non‐methylating ribonucleoprotein complexes: Old dogs show new tricks

Phylogenetic distribution of plant snoRNA families

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