Small nucleolar RNA

After transcription, nascent rRNA molecules (termed pre-rRNA) undergo a series of processing steps to generate the mature rRNA molecule. Prior to cleavage by exo- and endonucleases, the pre-rRNA undergoes a complex pattern of nucleoside modifications. These include methylations and pseudouridylations, guided by snoRNAs.

• Methylation is the attachment or substitution of a methyl group onto various substrates. The rRNA of humans contain approximately 115 methyl group modifications. The majority of these are 2′O-ribose-methylations (where the methyl group is attached to the ribose group).{{cite journal | vauthors = Maden BE, Hughes JM | title = Eukaryotic ribosomal RNA: the recent excitement in the nucleotide modification problem | journal = Chromosoma | volume = 105 | issue = 7–8 | pages = 391–400 | date = June 1997 | pmid = 9211966 | doi = 10.1007/BF02510475 | s2cid = 846233 }}
• Pseudouridylation is the conversion (isomerisation) of the nucleoside uridine to a different isomeric form pseudouridine (Ψ). This modification consists of a 180º rotation of the uridine base around its glycosyl bond to the ribose of the RNA backbone. After this rotation, the nitrogenous base contributes a carbon atom to the glycosyl bond instead of the usual nitrogen atom. The beneficial aspect of this modification is the additional hydrogen-bond donor available on the base. While uridine makes two hydrogen-bonds with its Watson-Crick base pair, adenine, pseudouridine is capable of making three hydrogen bonds. When pseudouridine is base-paired with adenine, it can also make another hydrogen bond, allowing the complexity of the mature rRNA structure to take form. The free hydrogen-bond donor often forms a bond with a base that is distant from itself, creating the tertiary structure that rRNA must have to be functional. Mature human rRNAs contain approximately 95 Ψ modifications.

Each snoRNA molecule acts as a guide for only one (or two) individual modifications in a target RNA.{{cite book | vauthors = Gjerde DT, Hoang L, Hornby D | chapter = Eurkaroytic Cellular DNA | title = RNA Purification and Analysis: Sample Preparation, Extraction, Chromatography |date=2009 |publisher=Wiley-VCH |location=Weinheim |isbn=978-3-527-62720-2 |pages=25–26 | chapter-url = https://books.google.com/books?id=qoshFRNUJS8C&pg=PA25 |access-date=28 September 2020}} In order to carry out modification, each snoRNA associates with at least four core proteins in an RNA/protein complex referred to as a small nucleolar ribonucleoprotein particle (snoRNP).{{cite book | vauthors = Bertrand E, Fournier MJ |title= Madame Curie Bioscience Database | chapter = The snoRNPs and Related Machines: Ancient Devices That Mediate Maturation of rRNA and Other RNAs | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK6107/ | location = Austin, Texas |publisher=Landes Bioscience |access-date=28 September 2020 |language=en |date=2013}} The proteins associated with each RNA depend on the type of snoRNA molecule (see snoRNA guide families below). The snoRNA molecule contains an antisense element (a stretch of 10–20 nucleotides), which are base complementary to the sequence surrounding the base (nucleotide) targeted for modification in the pre-RNA molecule. This enables the snoRNP to recognise and bind to the target RNA. Once the snoRNP has bound to the target site, the associated proteins are in the correct physical location to catalyse the chemical modification of the target base.{{cite journal | vauthors = Lykke-Andersen S, Ardal BK, Hollensen AK, Damgaard CK, Jensen TH | title = Box C/D snoRNP Autoregulation by a cis-Acting snoRNA in the NOP56 Pre-mRNA | journal = Molecular Cell | volume = 72 | issue = 1 | pages = 99–111.e5 | date = October 2018 | pmid = 30220559 | doi = 10.1016/j.molcel.2018.08.017 | doi-access = free }}

The two different types of rRNA modification (methylation and pseudouridylation) are directed by two different families of snoRNAs. These families of snoRNAs are referred to as antisense C/D box and H/ACA box snoRNAs based on the presence of conserved sequence motifs in the snoRNA. There are exceptions, but as a general rule C/D box members guide methylation and H/ACA members guide pseudouridylation. The members of each family may vary in biogenesis, structure, and function, but each family is classified by the following generalised characteristics. For more detail, see review.{{cite journal | vauthors = Bachellerie JP, Cavaillé J, Hüttenhofer A | title = The expanding snoRNA world | journal = Biochimie | volume = 84 | issue = 8 | pages = 775–790 | date = August 2002 | pmid = 12457565 | doi = 10.1016/S0300-9084(02)01402-5 }}

SnoRNAs are classified under small nuclear RNA in MeSH. The HGNC, in collaboration with [https://www-snorna.biotoul.fr/ snoRNABase] and experts in the field, has approved unique names for human genes that encode snoRNAs.{{cite journal | vauthors = Wright MW, Bruford EA | title = Naming 'junk': human non-protein coding RNA (ncRNA) gene nomenclature | journal = Human Genomics | volume = 5 | issue = 2 | pages = 90–98 | date = January 2011 | pmid = 21296742 | pmc = 3051107 | doi = 10.1186/1479-7364-5-2-90 | doi-access = free }}

File:RF00071.jpg database. This example is SNORD73 (RF00071).]]

C/D box snoRNAs contain two short conserved sequence motifs, C (RUGAUGA) and D (CUGA), located near the 5′ and 3′ ends of the snoRNA, respectively. Short regions (~ 5 nucleotides) located upstream of the C box and downstream of the D box are usually base complementary and form a stem-box structure, which brings the C and D box motifs into close proximity. This stem-box structure has been shown to be essential for correct snoRNA synthesis and nucleolar localization.{{cite journal | vauthors = Samarsky DA, Fournier MJ, Singer RH, Bertrand E | title = The snoRNA box C/D motif directs nucleolar targeting and also couples snoRNA synthesis and localization | journal = The EMBO Journal | volume = 17 | issue = 13 | pages = 3747–3757 | date = July 1998 | pmid = 9649444 | pmc = 1170710 | doi = 10.1093/emboj/17.13.3747 }} Many C/D box snoRNA also contain an additional less-well-conserved copy of the C and D motifs (referred to as C' and D') located in the central portion of the snoRNA molecule. A conserved region of 10–21 nucleotides upstream of the D box is complementary to the methylation site of the target RNA and enables the snoRNA to form an RNA duplex with the RNA.{{cite journal | vauthors = Kiss-László Z, Henry Y, Kiss T | title = Sequence and structural elements of methylation guide snoRNAs essential for site-specific ribose methylation of pre-rRNA | journal = The EMBO Journal | volume = 17 | issue = 3 | pages = 797–807 | date = February 1998 | pmid = 9451004 | pmc = 1170428 | doi = 10.1093/emboj/17.3.797 }} The nucleotide to be modified in the target RNA is usually located at the 5th position upstream from the D box (or D' box).{{cite journal | vauthors = Cavaillé J, Nicoloso M, Bachellerie JP | title = Targeted ribose methylation of RNA in vivo directed by tailored antisense RNA guides | journal = Nature | volume = 383 | issue = 6602 | pages = 732–735 | date = October 1996 | pmid = 8878486 | doi = 10.1038/383732a0 | bibcode = 1996Natur.383..732C | s2cid = 4334683 | doi-access = free }}{{cite journal | vauthors = Kiss-László Z, Henry Y, Bachellerie JP, Caizergues-Ferrer M, Kiss T | title = Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs | journal = Cell | volume = 85 | issue = 7 | pages = 1077–1088 | date = June 1996 | pmid = 8674114 | doi = 10.1016/S0092-8674(00)81308-2 | s2cid = 10418885 | doi-access = free }} C/D box snoRNAs associate with four evolutionary conserved and essential proteins—fibrillarin (Nop1p), NOP56, NOP58, and SNU13 (15.5-kD protein in eukaryotes; its archaeal homolog is L7Ae)—which make up the core C/D box snoRNP.

There exists a eukaryotic C/D box snoRNA (snoRNA U3) that has not been shown to guide 2′-O-methylation.

Instead, it functions in rRNA processing by directing pre-rRNA cleavage.

File:RF00265.jpg (RF00265).]]

H/ACA box snoRNAs have a common secondary structure consisting of a two hairpins and two single-stranded regions termed a hairpin-hinge-hairpin-tail structure. H/ACA snoRNAs also contain conserved sequence motifs known as H box (consensus ANANNA) and the ACA box (ACA). Both motifs are usually located in the single-stranded regions of the secondary structure. The H motif is located in the hinge and the ACA motif is located in the tail region; 3 nucleotides from the 3′ end of the sequence.{{cite journal | vauthors = Ganot P, Caizergues-Ferrer M, Kiss T | title = The family of box ACA small nucleolar RNAs is defined by an evolutionarily conserved secondary structure and ubiquitous sequence elements essential for RNA accumulation | journal = Genes & Development | volume = 11 | issue = 7 | pages = 941–956 | date = April 1997 | pmid = 9106664 | doi = 10.1101/gad.11.7.941 | doi-access = free }} The hairpin regions contain internal bulges known as recognition loops in which the antisense guide sequences (bases complementary to the target sequence) are located. These guide sequences essentially mark the location of the uridine on the target rRNA that is going to be modified. This recognition sequence is bipartite (constructed from the two different arms of the loop region) and forms complex pseudo-knots with the target RNA. H/ACA box snoRNAs associate with four evolutionary conserved and essential proteins—dyskerin (Cbf5p), GAR1, NHP2, and NOP10—which make up the core of the H/ACA box snoRNP. Dyskerin is likely the catalytic component of the ribonucleoprotein (RNP) complex because it possesses several conserved pseudouridine synthase sequences, and is closely related to the pseudouridine synthase that modifies uridine in tRNA. In lower eukaryotic cells such as trypanosomes, similar RNAs exist in the form of single hairpin structure and an AGA box instead of ACA box at the 3′ end of the RNA.{{cite journal | vauthors = Liang XH, Liu L, Michaeli S | title = Identification of the first trypanosome H/ACA RNA that guides pseudouridine formation on rRNA | journal = The Journal of Biological Chemistry | volume = 276 | issue = 43 | pages = 40313–40318 | date = October 2001 | pmid = 11483606 | doi = 10.1074/jbc.M104488200 | doi-access = free }} Like Trypanosomes, Entamoeba histolytica has mix population of single hairpin as well as double hairpin H/ACA box snoRNAs. It was reported that there occurred processing of the double hairpin H/ACA box snoRNA to the single hairpin snoRNAs however, unlike trypanosomes, it has a regular ACA motif at 3′ tail.^[19]

The RNA component of human telomerase (hTERC) contains an H/ACA domain for pre-RNP formation and nucleolar localization of the telomerase RNP itself.{{cite journal | vauthors = Trahan C, Dragon F | title = Dyskeratosis congenita mutations in the H/ACA domain of human telomerase RNA affect its assembly into a pre-RNP | journal = RNA | volume = 15 | issue = 2 | pages = 235–243 | date = February 2009 | pmid = 19095616 | pmc = 2648702 | doi = 10.1261/rna.1354009 }} The H/ACA snoRNP has been implicated in the rare genetic disease dyskeratosis congenita (DKC) due to its affiliation with human telomerase. Mutations in the protein component of the H/ACA snoRNP result in a reduction in physiological TERC levels. This has been strongly correlated with the pathology behind DKC, which seems to be primarily a disease of poor telomere maintenance.

An unusual guide snoRNA U85 that functions in both 2′-O-ribose methylation and pseudouridylation of small nuclear RNA (snRNA) U5 has been identified.{{cite journal | vauthors = Jády BE, Kiss T | title = A small nucleolar guide RNA functions both in 2′-O-ribose methylation and pseudouridylation of the U5 spliceosomal RNA | journal = The EMBO Journal | volume = 20 | issue = 3 | pages = 541–551 | date = February 2001 | pmid = 11157760 | pmc = 133463 | doi = 10.1093/emboj/20.3.541 }} This composite snoRNA contains both C/D and H/ACA box domains and associates with the proteins specific to each class of snoRNA (fibrillarin and Gar1p, respectively). More composite snoRNAs have now been characterised.{{cite journal | vauthors = Darzacq X, Jády BE, Verheggen C, Kiss AM, Bertrand E, Kiss T | title = Cajal body-specific small nuclear RNAs: a novel class of 2′-O-methylation and pseudouridylation guide RNAs | journal = The EMBO Journal | volume = 21 | issue = 11 | pages = 2746–2756 | date = June 2002 | pmid = 12032087 | pmc = 126017 | doi = 10.1093/emboj/21.11.2746 }}

These composite snoRNAs have been found to accumulate in a subnuclear organelle called the Cajal body and are referred to as small Cajal body-specific RNAs (scaRNAs). This is in contrast to the majority of C/D box or H/ACA box snoRNAs, which localise to the nucleolus. These Cajal body specific RNAs are proposed to be involved in the modification of RNA polymerase II transcribed spliceosomal RNAs U1, U2, U4, U5 and U12. Not all snoRNAs that have been localised to Cajal bodies are composite C/D and H/ACA box snoRNAs.

The targets for newly identified snoRNAs are predicted on the basis of sequence complementarity between putative target RNAs and the antisense elements or recognition loops in the snoRNA sequence. However, there are increasing numbers of 'orphan' guides without any known RNA targets, which suggests that there might be more proteins or transcripts involved in rRNA than previously and/or that some snoRNAs have different functions not concerning rRNA.{{cite journal | vauthors = Jády BE, Kiss T | title = Characterisation of the U83 and U84 small nucleolar RNAs: two novel 2′-O-ribose methylation guide RNAs that lack complementarities to ribosomal RNAs | journal = Nucleic Acids Research | volume = 28 | issue = 6 | pages = 1348–1354 | date = March 2000 | pmid = 10684929 | pmc = 111033 | doi = 10.1093/nar/28.6.1348 | url = | format = Free full text }}{{cite journal | vauthors = Li SG, Zhou H, Luo YP, Zhang P, Qu LH | title = Identification and functional analysis of 20 Box H/ACA small nucleolar RNAs (snoRNAs) from Schizosaccharomyces pombe | journal = The Journal of Biological Chemistry | volume = 280 | issue = 16 | pages = 16446–16455 | date = April 2005 | pmid = 15716270 | doi = 10.1074/jbc.M500326200 | doi-access = free }} There is evidence that some of these orphan snoRNAs regulate alternatively spliced transcripts.{{cite journal | vauthors = Kishore S, Stamm S | title = Regulation of alternative splicing by snoRNAs | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 71 | pages = 329–334 | year = 2006 | pmid = 17381313 | doi = 10.1101/sqb.2006.71.024 | doi-access = free }} For example, it appears that the C/D box snoRNA SNORD115 regulates the alternative splicing of the serotonin 2C receptor mRNA via a conserved region of complementarity.{{cite journal | vauthors = Kishore S, Stamm S | title = The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C | journal = Science | volume = 311 | issue = 5758 | pages = 230–232 | date = January 2006 | pmid = 16357227 | doi = 10.1126/science.1118265 | bibcode = 2006Sci...311..230K | s2cid = 44527461 | doi-access = free }}{{cite journal | vauthors = Doe CM, Relkovic D, Garfield AS, Dalley JW, Theobald DE, Humby T, Wilkinson LS, Isles AR | title = Loss of the imprinted snoRNA mbii-52 leads to increased 5htr2c pre-RNA editing and altered 5HT2CR-mediated behaviour | journal = Human Molecular Genetics | volume = 18 | issue = 12 | pages = 2140–2148 | date = June 2009 | pmid = 19304781 | pmc = 2685753 | doi = 10.1093/hmg/ddp137 }}

Another C/D box snoRNA, SNORD116, that resides in the same cluster as SNORD115 has been predicted to have 23 possible targets within protein coding genes using a bioinformatic approach. Of these, a large fraction were found to be alternatively spliced, suggesting a role of SNORD116 in the regulation of alternative splicing.{{cite journal | vauthors = Bazeley PS, Shepelev V, Talebizadeh Z, Butler MG, Fedorova L, Filatov V, Fedorov A | title = snoTARGET shows that human orphan snoRNA targets locate close to alternative splice junctions | journal = Gene | volume = 408 | issue = 1–2 | pages = 172–179 | date = January 2008 | pmid = 18160232 | pmc = 6800007 | doi = 10.1016/j.gene.2007.10.037 }}

More recently, SNORD90 has been suggested to be able to guide N6-methyladenosine (m6A) modifications onto target RNA transcripts.{{cite journal | vauthors = Lin R, Kos A, Lopez JP, Dine J, Fiori LM, Yang J, Ben-Efraim Y, Aouabed Z, Ibrahim P, Mitsuhashi H, Wong TP, Ibrahim EC, Belzung C, Blier P, Farzan F, Frey BN, Lam RW, Milev R, Muller DJ, Parikh SV, Soares C, Uher R, Nagy C, Mechawar N, Foster JA, Kennedy SH, Chen A, Turecki G | display-authors = 6 | title = SNORD90 induces glutamatergic signaling following treatment with monoaminergic antidepressants | journal = eLife | volume = 12 | pages = e85316 | date = July 2023 | pmid = 37432876 | pmc = 10335830 | doi = 10.7554/eLife.85316 | veditors = West AE, Wong ML | doi-access = free }} More specifically, Lin et al. demonstrated that SNORD90 can reduce the expression of neuregulin 3 (NRG3).

The precise effect of the methylation and pseudouridylation modifications on the function of the mature RNAs is not yet known. The modifications do not appear to be essential but are known to subtly enhance the RNA folding and interaction with ribosomal proteins. In support of their importance, target site modifications are exclusively located within conserved and functionally important domains of the mature RNA and are commonly conserved among distant eukaryotes. A novel method, Nm-REP-seq, was developed for enriching 2'-O-Methylations guided by C/D snoRNAs by using RNA exoribonuclease (Mycoplasma genitalium RNase R, MgR) and periodate oxidation reactivity to eliminate 2'-hydroxylated (2'-OH) nucleosides.{{cite journal | vauthors = Zhang P, Huang J, Zheng W, Chen L, Liu S, Liu A, Ye J, Zhou J, Chen Z, Huang Q, Liu S, Zhou K, Qu L, Li B, Yang J | display-authors = 6 | title = Single-base resolution mapping of 2'-O-methylation sites by an exoribonuclease-enriched chemical method | journal = Science China Life Sciences | volume = 66 | issue = 4 | pages = 800–818 | date = April 2023 | pmid = 36323972 | doi = 10.1007/s11427-022-2210-0 | s2cid = 253266867 }}

1. 2′-O-methylated ribose causes an increase in the 3′-endo conformation
2. Pseudouridine (psi/Ψ) adds another option for H-bonding.
3. Heavily methylated RNA is protected from hydrolysis. rRNA acts as a ribozyme by catalyzing its own hydrolysis and splicing.

SnoRNAs are located diversely in the genome. The majority of vertebrate snoRNA genes are encoded in the introns of genes encoding proteins involved in ribosome synthesis or translation, and are synthesized by RNA polymerase II. SnoRNAs are also shown to be located in intergenic regions, ORFs of protein coding genes, and UTRs.{{cite journal | vauthors = Kaur D, Gupta AK, Kumari V, Sharma R, Bhattacharya A, Bhattacharya S | date = 14 August 2012 | title = Computational prediction and validation of C/D, H/ACA and Eh_U3 snoRNAs of Entamoeba histolytica | journal = BMC Genomics | volume = 13 | page = 390 | doi = 10.1186/1471-2164-13-390 | pmid = 22892049 | pmc = 3542256 | doi-access = free }} SnoRNAs can also be transcribed from their own promoters by RNA polymerase II or III.

In the human genome, there are at least two examples where C/D box snoRNAs are found in tandem repeats within imprinted loci. These two loci (14q32 on chromosome 14 and 15q11q13 on chromosome 15) have been extensively characterised, and in both regions multiple snoRNAs have been found located within introns in clusters of closely related copies.

In 15q11q13, five different snoRNAs have been identified (SNORD64, SNORD107, SNORD108, SNORD109 (two copies), SNORD116 (29 copies) and SNORD115 (48 copies). Loss of the 29 copies of SNORD116 (HBII-85) from this region has been identified as a cause of Prader-Willi syndrome{{cite journal | vauthors = Skryabin BV, Gubar LV, Seeger B, Pfeiffer J, Handel S, Robeck T, Karpova E, Rozhdestvensky TS, Brosius J | title = Deletion of the MBII-85 snoRNA gene cluster in mice results in postnatal growth retardation | journal = PLOS Genetics | volume = 3 | issue = 12 | pages = e235 | date = December 2007 | pmid = 18166085 | pmc = 2323313 | doi = 10.1371/journal.pgen.0030235 | doi-access = free }}{{cite journal | vauthors = Sahoo T, del Gaudio D, German JR, Shinawi M, Peters SU, Person RE, Garnica A, Cheung SW, Beaudet AL | title = Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster | journal = Nature Genetics | volume = 40 | issue = 6 | pages = 719–721 | date = June 2008 | pmid = 18500341 | pmc = 2705197 | doi = 10.1038/ng.158 }}{{cite journal | vauthors = Ding F, Li HH, Zhang S, Solomon NM, Camper SA, Cohen P, Francke U | title = SnoRNA Snord116 (Pwcr1/MBII-85) deletion causes growth deficiency and hyperphagia in mice | journal = PLOS ONE | volume = 3 | issue = 3 | pages = e1709 | date = March 2008 | pmid = 18320030 | pmc = 2248623 | doi = 10.1371/journal.pone.0001709 | veditors = Akbarian S | bibcode = 2008PLoSO...3.1709D | doi-access = free }}{{cite journal | vauthors = Ding F, Prints Y, Dhar MS, Johnson DK, Garnacho-Montero C, Nicholls RD, Francke U | title = Lack of Pwcr1/MBII-85 snoRNA is critical for neonatal lethality in Prader-Willi syndrome mouse models | journal = Mammalian Genome | volume = 16 | issue = 6 | pages = 424–431 | date = June 2005 | pmid = 16075369 | doi = 10.1007/s00335-005-2460-2 | s2cid = 12256515 }} whereas gain of additional copies of SNORD115 has been linked to autism.{{cite journal | vauthors = Nakatani J, Tamada K, Hatanaka F, Ise S, Ohta H, Inoue K, Tomonaga S, Watanabe Y, Chung YJ, Banerjee R, Iwamoto K, Kato T, Okazawa M, Yamauchi K, Tanda K, Takao K, Miyakawa T, Bradley A, Takumi T | title = Abnormal behavior in a chromosome-engineered mouse model for human 15q11–13 duplication seen in autism | journal = Cell | volume = 137 | issue = 7 | pages = 1235–1246 | date = June 2009 | pmid = 19563756 | pmc = 3710970 | doi = 10.1016/j.cell.2009.04.024 }}{{cite journal | vauthors = Bolton PF, Veltman MW, Weisblatt E, Holmes JR, Thomas NS, Youings SA, Thompson RJ, Roberts SE, Dennis NR, Browne CE, Goodson S, Moore V, Brown J | title = Chromosome 15q11–13 abnormalities and other medical conditions in individuals with autism spectrum disorders | journal = Psychiatric Genetics | volume = 14 | issue = 3 | pages = 131–137 | date = September 2004 | pmid = 15318025 | doi = 10.1097/00041444-200409000-00002 | s2cid = 37344935 }}{{cite journal | vauthors = Cook EH, Scherer SW | title = Copy-number variations associated with neuropsychiatric conditions | journal = Nature | volume = 455 | issue = 7215 | pages = 919–923 | date = October 2008 | pmid = 18923514 | doi = 10.1038/nature07458 | bibcode = 2008Natur.455..919C | s2cid = 4377899 }}

Region 14q32 contains repeats of two snoRNAs SNORD113 (9 copies) and SNORD114 (31 copies) within the introns of a tissue-specific ncRNA transcript (MEG8). The 14q32 domain has been shown to share common genomic features with the imprinted 15q11-q13 loci and a possible role for tandem repeats of C/D box snoRNAs in the evolution or mechanism of imprinted loci has been suggested.{{cite journal | vauthors = Cavaillé J, Seitz H, Paulsen M, Ferguson-Smith AC, Bachellerie JP | title = Identification of tandemly-repeated C/D snoRNA genes at the imprinted human 14q32 domain reminiscent of those at the Prader-Willi/Angelman syndrome region | journal = Human Molecular Genetics | volume = 11 | issue = 13 | pages = 1527–1538 | date = June 2002 | pmid = 12045206 | doi = 10.1093/hmg/11.13.1527 | doi-access = free }}{{cite journal | vauthors = Labialle S, Cavaillé J | title = Do repeated arrays of regulatory small-RNA genes elicit genomic imprinting?: Concurrent emergence of large clusters of small non-coding RNAs and genomic imprinting at four evolutionarily distinct eutherian chromosomal loci | journal = BioEssays | volume = 33 | issue = 8 | pages = 565–573 | date = August 2011 | pmid = 21618561 | doi = 10.1002/bies.201100032 | s2cid = 10408004 }}

snoRNAs can function as miRNAs. It has been shown that human ACA45 is a bona fide snoRNA that can be processed into a 21-nucleotides-long mature miRNA by the RNAse III family endoribonuclease dicer.{{cite journal | vauthors = Ender C, Krek A, Friedländer MR, Beitzinger M, Weinmann L, Chen W, Pfeffer S, Rajewsky N, Meister G | title = A human snoRNA with microRNA-like functions | journal = Molecular Cell | volume = 32 | issue = 4 | pages = 519–528 | date = November 2008 | pmid = 19026782 | doi = 10.1016/j.molcel.2008.10.017 | doi-access = free }} This snoRNA product has previously been identified as [http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0009991 mmu-miR-1839] and was shown to be processed independently from the other miRNA-generating endoribonuclease drosha.{{cite journal | vauthors = Babiarz JE, Ruby JG, Wang Y, Bartel DP, Blelloch R | title = Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs | journal = Genes & Development | volume = 22 | issue = 20 | pages = 2773–2785 | date = October 2008 | pmid = 18923076 | pmc = 2569885 | doi = 10.1101/gad.1705308 }} Bioinformatical analyses have revealed that putatively snoRNA-derived, miRNA-like fragments occur in different organisms.{{cite journal | vauthors = Taft RJ, Glazov EA, Lassmann T, Hayashizaki Y, Carninci P, Mattick JS | title = Small RNAs derived from snoRNAs | journal = RNA | volume = 15 | issue = 7 | pages = 1233–1240 | date = July 2009 | pmid = 19474147 | pmc = 2704076 | doi = 10.1261/rna.1528909 }}

Recently, it has been found that snoRNAs can have functions not related to rRNA. One such function is the regulation of alternative splicing of the trans gene transcript, which is done by the snoRNA HBII-52, which is also known as SNORD115.

In November 2012, Schubert et al. revealed that specific RNAs control chromatin compaction and accessibility in Drosophila cells.{{cite journal | vauthors = Schubert T, Pusch MC, Diermeier S, Benes V, Kremmer E, Imhof A, Längst G | title = Df31 protein and snoRNAs maintain accessible higher-order structures of chromatin | journal = Molecular Cell | volume = 48 | issue = 3 | pages = 434–444 | date = November 2012 | pmid = 23022379 | doi = 10.1016/j.molcel.2012.08.021 | doi-access = free }}

In July 2023, Lin et al. showed that snoRNAs have the potential to guide other RNA modifications, specifically N6-methyladenosine, however this is subject to further investigation.

TB11Cs4H1 is a member of the H/ACA-like class of non-coding RNA (ncRNA) molecule (a snoRNA) that guide the sites of modification of uridines to pseudouridines of substrate RNAs. TB11Cs4H1 is predicted to guide the pseudouridylation of LSU3 ribosomal RNA (rRNA) at residue Ψ1357.{{cite journal|vauthors=Liang XH, Uliel S, Hury A, Barth S, Doniger T, Unger R, Michaeli S |title=A genome-wide analysis of C/D and H/ACA-like small nucleolar RNAs in Trypanosoma brucei reveals a trypanosome-specific pattern of rRNA modification.|journal=RNA|date=May 2005|volume=11|issue=5|pages=619–645|pmid=15840815|doi=10.1261/rna.7174805|pmc=1370750}}

{{reflist|2}}

• [https://web.archive.org/web/20091220034028/http://deepbase.sysu.edu.cn/prediction.php human snoRNA atlas from small RNA sequencing data]
• [http://bioinf.scri.sari.ac.uk/cgi-bin/plant_snorna/home plant snoRNA database]
• [https://web.archive.org/web/20070827132008/http://www-snorna.biotoul.fr/ snoRNAbase: human H/ACA and C/D box snoRNA database]
• [https://web.archive.org/web/20081120083220/http://evolveathome.com/snoRNA/snoRNA.php snoRNP Database]
• [http://people.biochem.umass.edu/fournierlab/snornadb/main.php The yeast snoRNA database]
• [https://web.archive.org/web/20160425064857/http://biocenter.sysu.edu.cn/deepBase/browser_smallRNA.php?SClade=mammal&SOrganism=hg19&SSource=GSE20592 human snoRNA expression pattern]
• [http://rfam.org/search?q=entry_type:%22Family%22%20AND%20rna_type:%22CD-box%22 Rfam page for C/D box snoRNAs]
• [http://rfam.org/search?q=entry_type:%22Family%22%20AND%20rna_type:%22HACA-box%22 Rfam page for H/ACA box snoRNAs]
• [http://rfam.org/search?q=entry_type:%22Family%22%20AND%20rna_type:%22scaRNA%22 Rfam page for scaRNA snoRNAs]

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{{Small nucleolar RNA}}

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