The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing

Kishore, Shivendra; Khanna, Amit; Zhang, Zhaiyi; Hui, Jingyi; Balwierz, Piotr J.; Stefan, Mihaela; Beach, Carol M.; Nicholls, Robert D.; Zavolan, Mihaela; Stamm, Stefan

doi:10.1093/hmg/ddp585

Cited by 260 publications

(293 citation statements)

References 34 publications

Supporting

Mentioning

281

Contrasting

Unclassified

Order By: Relevance

“…The presence of SNORD27 in nuclear fractions devoid of fibrillarin suggests that it has a function apart from rRNA 2′-O-methylation. We previously found that the orphan SNORD115 changes alternative splicing of the serotonin receptor 2C and several other premRNAs, possibly through base pairing of SNORD115 to a splicing regulatory region (31,51). We, therefore, looked for complementarities between SNORD27 and pre-mRNAs across the genome.…”

Section: Resultsmentioning

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.

Self Cite

171

152

View full text Add to dashboard Cite

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 ...

show abstract

Section: Resultsmentioning

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.

Self Cite

171

152

View full text Add to dashboard Cite

show abstract

“…3 Recent new cellular functions have led us to hypothesize that snoRNA accumulation patterns could be modulated in cancer. [10][11][12]14,[30][31][32][33][34][35] Acute leukemia is a good model to try to answer this question as it is characterized by restrictive oncogenic events leading to a blockade in differentiation.…”

Section: Discussionmentioning

confidence: 99%

Specific small nucleolar RNA expression profiles in acute leukemia

et al. 2012

View full text Add to dashboard Cite

Apart from microRNAs, little is known about the regulation of expression of non-coding RNAs in cancer. We investigated whether small nucleolar RNAs (snoRNAs) accumulation displayed specific signatures in acute myeloblastic and acute lymphoblastic leukemias. Using microarrays and high-throughput quantitative PCR (qPCR), we demonstrate here that snoRNA expression patterns are negatively altered in leukemic cells compared with controls. Interestingly, a specific signature was found in acute promyelocytic leukemia (APL) with ectopic expression of SNORD112-114 snoRNAs located at the DLK1-DIO3 locus. In vitro experiments carried out on APL blasts demonstrate that transcription of these snoRNAs was lost under all-trans retinoic acid-mediated differentiation and induced by enforced expression of the PML-RARalpha fusion protein in negative leukemic cell lines. Further experiments revealed that the SNORD114-1 (14q(II-1)) variant promoted cell growth through cell cycle modulation; its expression was implicated in the G0/G1 to S phase transition mediated by the Rb/p16 pathways. This study thus reports three important observations: (1) snoRNA regulation is different in normal cells compared with cancer cells; (2) a relationship exists between a chromosomal translocation and expression of snoRNA loci; and (3) snoRNA expression can affect Rb/p16 cell cycle regulation. Taken together, these data strongly suggest that snoRNAs have a role in cancer development.

show abstract

“…Although the main function of snoRNA is to guide chemical modifications of other RNAs, some of them or their fragments can regulate splicing or translation (Kishore et al 2010;Scott et al 2012;Stepanov et al 2012). While some (in particular, H/ACA box) snoRNAs interact with their rRNA targets by small bipartite recognition sites, the known cases of splicing regulation contain long, uninterrupted helices.…”

Section: Snorna Targetsmentioning

confidence: 99%

IRBIS: a systematic search for conserved complementarity

Pervouchine¹

2014

RNA

View full text Add to dashboard Cite

IRBIS is a computational pipeline for detecting conserved complementary regions in unaligned orthologous sequences. Unlike other methods, it follows the "first-fold-then-align" principle in which all possible combinations of complementary k-mers are searched for simultaneous conservation. The novel trimming procedure reduces the size of the search space and improves the performance to the point where large-scale analyses of intra-and intermolecular RNA-RNA interactions become possible. In this article, I provide a rigorous description of the method, benchmarking on simulated and real data, and a set of stringent predictions of intramolecular RNA structure in placental mammals, drosophilids, and nematodes. I discuss two particular cases of long-range RNA structures that are likely to have a causal effect on single-and multiple-exon skipping, one in the mammalian gene Dystonin and the other in the insect gene Ca-α 1 D. In Dystonin, one of the two complementary boxes contains a binding site of Rbfox protein similar to one recently described in Enah gene. I also report that snoRNAs and long noncoding RNAs (lncRNAs) have a high capacity of base-pairing to introns of protein-coding genes, suggesting possible involvement of these transcripts in splicing regulation. I also find that conserved sequences that occur equally likely on both strands of DNA (e.g., transcription factor binding sites) contribute strongly to the false-discovery rate and, therefore, would confound every such analysis. IRBIS is an open-source software that is available at

show abstract

The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing

Cited by 260 publications

References 34 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

Specific small nucleolar RNA expression profiles in acute leukemia

IRBIS: a systematic search for conserved complementarity

Contact Info

Product

Resources

About