The noncoding RNAs SNORD50A and SNORD50B bind K-Ras and are recurrently deleted in human cancer

Siprashvili, Zurab; Webster, Dan E.; Johnston, Danielle; Shenoy, Rajani Marthappa; Ungewickell, Alexander; Bhaduri, Aparna; Flockhart, Ross J.; Zarnegar, Brian; Che, Yonglu; Meschi, Francesca; Puglisi, Joseph D.; Khavari, Paul A.

doi:10.1038/ng.3452

Cited by 153 publications

(150 citation statements)

References 31 publications

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“…Whereas snoRNAs of the C/D box family are well-known to guide fibrillarin-mediated 2′O methylation of the ribosomal RNA, reduced expression and both somatic and germ line mutations in U50 have been reported from breast and prostate cancer3031. Furthermore, a non-canonical function of the U50 snoRNA in modulating RAS activity was recently described32. Although currently unclear, this is likely independent from the SNHG5 mechanism characterized in this paper.…”

Section: Discussionmentioning

confidence: 63%

SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization

et al. 2016

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We currently have limited knowledge of the involvement of long non-coding RNAs (lncRNAs) in normal cellular processes and pathologies. Here, we identify and characterize SNHG5 as a stable cytoplasmic lncRNA with up-regulated expression in colorectal cancer. Depletion of SNHG5 induces cell cycle arrest and apoptosis in vitro and limits tumour outgrowth in vivo, whereas SNHG5 overexpression counteracts oxaliplatin-induced apoptosis. Using an unbiased approach, we identify 121 transcript sites interacting with SNHG5 in the cytoplasm. Importantly, knockdown of key SNHG5 target transcripts, including SPATS2, induces apoptosis and thus mimics the effect seen following SNHG5 depletion. Mechanistically, we suggest that SNHG5 stabilizes the target transcripts by blocking their degradation by STAU1. Accordingly, depletion of STAU1 rescues the apoptosis induced after SNHG5 knockdown. Hence, we characterize SNHG5 as a lncRNA promoting tumour cell survival in colorectal cancer and delineate a novel mechanism in which a cytoplasmic lncRNA functions through blocking the action of STAU1.

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Section: Discussionmentioning

confidence: 63%

SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization

et al. 2016

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“…For example, emerging data suggest that snoRNAs may contribute to alternative splicing, 7 regulation of chromatin structure, 8 metabolism, 9 and neoplastic transformation. 10 The contribution of snoRNAs to the regulation of normal and malignant hematopoiesis is largely unknown. Chu et al reported that overexpression of the H/ACA box snoRNA ACA11 in t(4;14)-associated multiple myeloma contributes to myeloma cell proliferation and resistance to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Expression profiling of snoRNAs in normal hematopoiesis and AML

Warner¹,

Spencer

Trissal³

et al. 2018

Blood Advances

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Key Points• A subset of snoRNAs is expressed in a developmental-and lineage-specific manner during human hematopoiesis.• Neither host gene expression nor alternative splicing accounted for the observed differential expression of snoRNAs in a subset of AML.Small nucleolar RNAs (snoRNAs) are noncoding RNAs that contribute to ribosome biogenesis and RNA splicing by modifying ribosomal RNA and spliceosome RNAs, respectively. We optimized a next-generation sequencing approach and a custom analysis pipeline to identify and quantify expression of snoRNAs in acute myeloid leukemia (AML) and normal hematopoietic cell populations. We show that snoRNAs are expressed in a lineage-and development-specific fashion during hematopoiesis. The most striking examples involve snoRNAs located in 2 imprinted loci, which are highly expressed in hematopoietic progenitors and downregulated during myeloid differentiation. Although most snoRNAs are expressed at similar levels in AML cells compared with CD34 1 , a subset of snoRNAs showed consistent differential expression, with the great majority of these being decreased in the AML samples. Analysis of host gene expression, splicing patterns, and whole-genome sequence data for mutational events did not identify transcriptional patterns or genetic alterations that account for these expression differences. These data provide a comprehensive analysis of the snoRNA transcriptome in normal and leukemic cells and should be helpful in the design of studies to define the contribution of snoRNAs to normal and malignant hematopoiesis.

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“…Although SNORDs are considered housekeeping genes, the expression of some SNORDs is altered in cancer. 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%

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.

165

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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The noncoding RNAs SNORD50A and SNORD50B bind K-Ras and are recurrently deleted in human cancer

Cited by 153 publications

References 31 publications

SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization

SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization

Expression profiling of snoRNAs in normal hematopoiesis and AML

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

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