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Zhisu Liu - One of the best experts on this subject based on the ideXlab platform.

  • The C/D box Small Nucleolar RNA SNORD52 regulated by Upf1 facilitates Hepatocarcinogenesis by stabilizing CDK1.
    Theranostics, 2020
    Co-Authors: Pengpeng Liu, Quanyan Liu, Zhonglin Zhang, Ping Jiang, Zhiyong Yang, Zhisu Liu
    Abstract:

    Rationale: Understanding the roles of Small Nucleolar RNAs (snoRNAs) in hepatocarcinogenesis will provide new avenues to identify diagnostic and therapeutic targets for hepatocellular carcinoma (HCC). Our previous research confirmed the tumor-suppressive effect of Up-frameshift 1 (Upf1) in HCC. Herein, we examined the expression profiles of snoRNAs regulated by Upf1 in hepatoma cells. Methods: We examined the expression profiles of snoRNAs regulated by Upf1 in hepatoma cells using RNA-sequencing analysis and then investigated the expression and significance of SNORD52 in HCC tissue and different cell lines. The protumorigenic effects of SNORD52 on HCC cells were confirmed both in vitro and in vivo by gain-of-function and loss-of-function assays. RNA pull-down assays and mass spectrometry were used to identify the RNA-binding protein that binds to SNORD52. Results: Many snoRNAs were identified; one of which, the human C/D box Small Nucleolar RNA SNORD52, was upregulated in HCC tissues and negatively correlated with Upf1 expression, and patients with higher SNORD52 expression had a poor clinical prognosis. SNORD52 promoted HCC tumorigenesis both in vitro and in vivo. Mechanistically, KEGG analysis showed that SNORD52 upregulated a series of cell cycle genes in HCC cells. We further confirmed that SNORD52 upregulated CDK1 by enhancing the stability of CDK1 proteins and that the function of SNORD52 depends on the presence of CDK1. Conclusion: Overall, the present study indicates that SNORD52 could be a potential biomarker for HCC. Targeting the Upf1/SNORD52/CDK1 pathway might have therapeutic potential for HCC.

  • Small Nucleolar RNA u2_19 promotes hepatocellular carcinoma progression by regulating wnt β catenin signaling
    Biochemical and Biophysical Research Communications, 2018
    Co-Authors: Haitao Wang, Pengpeng Liu, Baiyang Chen, Zhisu Liu
    Abstract:

    Abstract Emerging evidence suggests that Small Nucleolar RNAs (snoRNAs) have malfunctioning roles in oncogenesis. In the present study, we investigated the role of box C/D Small Nucleolar RNA U2_19 (snoU2_19) in the tumorigenesis of hepatocellular carcinoma (HCC). Recently, we screened snoRNAs differential signatures by performing high-throughput Small RNA sequence in HCC tissues and validated that upregulated snoU2_19 was associated with aggressive phenotypes in HCC patients. Aberrant snoU2_19 facilitated HCC cell proliferation, inhibited apoptosis and induced cell cycle progression in vitro analyses. We globally investigated the molecular mechanisms of snoU2_19 in HCC and found that snoU2_19 knockdown inhibited Wnt/β-catenin signaling pathway through inducing the translocation of β-catenin in cytoplasm. We concluded that snoU2_19 plays a pathological role in the development and progression of HCC, and is a potential therapeutic target for HCC.

  • Small Nucleolar RNA U2_19 promotes hepatocellular carcinoma progression by regulating Wnt/β-catenin signaling
    Biochemical and biophysical research communications, 2018
    Co-Authors: Haitao Wang, Pengpeng Liu, Baiyang Chen, Zhisu Liu
    Abstract:

    Abstract Emerging evidence suggests that Small Nucleolar RNAs (snoRNAs) have malfunctioning roles in oncogenesis. In the present study, we investigated the role of box C/D Small Nucleolar RNA U2_19 (snoU2_19) in the tumorigenesis of hepatocellular carcinoma (HCC). Recently, we screened snoRNAs differential signatures by performing high-throughput Small RNA sequence in HCC tissues and validated that upregulated snoU2_19 was associated with aggressive phenotypes in HCC patients. Aberrant snoU2_19 facilitated HCC cell proliferation, inhibited apoptosis and induced cell cycle progression in vitro analyses. We globally investigated the molecular mechanisms of snoU2_19 in HCC and found that snoU2_19 knockdown inhibited Wnt/β-catenin signaling pathway through inducing the translocation of β-catenin in cytoplasm. We concluded that snoU2_19 plays a pathological role in the development and progression of HCC, and is a potential therapeutic target for HCC.

  • Up-regulation of Small Nucleolar RNA 78 is correlated with aggressive phenotype and poor prognosis of hepatocellular carcinoma.
    Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016
    Co-Authors: Haitao Wang, Lu Han, Wei Jing, Xin Zhou, Zhisu Liu
    Abstract:

    Small Nucleolar RNAs (snoRNAs) as a novel molecular species may have significant and comprehensive influences on the development and progression of hepatocellular carcinoma (HCC). We recently characterized snoRNA transcriptome signatures in HCC tissues by Small RNA sequencing and found that Small Nucleolar RNA 78 (SNORD78) was associated with HCC. However, little is known about the pathological role of SNORD78 in HCC patients. This study aimed to profile SNORD78 expression signature and then to explore the pathogenesis of SNORD78 in HCC. The real-time PCR results showed that SNORD78 was greatly upregulated in HCC tissues than adjacent noncancerous tissues (p = 0.004). Correlation analysis showed that high-level expression of SNORD78 was notably associated with tumor number (single vs. multiply, p = 0.02), stage (I∼II vs. III∼IV, p = 0.014), and distant metastasis (absent vs. present, p = 0.01) in HCC patients. Univatiate and multivariate analyses showed that SNORD78 was a significant prognostic predictor for overall survival and recurrence-free survival of HCC patients (hazard ratio = 1.375, 95 % CI = 1.125–1.680, p = 0.002; hazard ratio = 1.418, 95 % CI = 1.201–1.675, p < 0.001). Moreover, Kaplan-Meier analysis showed that high-level expression of SNORD78 was associated with short overall survival and recurrence-free survival of HCC patients (p = 0.023, 0.014). Functionally, knockdown of SNORD78 significantly inhibited cellular proliferation, migration, and invasion of SK-Hep-1 via inducing G0/G1 cell cycle arrest and apoptosis. In conclusion, SNORD78 may be associated with aggressive phenotype and poor prognosis of HCC.

Maurille J. Fournier - One of the best experts on this subject based on the ideXlab platform.

  • a Small Nucleolar RNA ribozyme hybrid cleaves a Nucleolar RNA target in vivo with near perfect efficiency
    Proceedings of the National Academy of Sciences of the United States of America, 1999
    Co-Authors: Dmitry Samarsky, Gerardo Ferbeyre, Edouard Bertrand, Robert H Singer, Robert Cedergren, Maurille J. Fournier
    Abstract:

    A hammerhead ribozyme has been localized to the yeast nucleolus by using the U3 Small Nucleolar RNA as a carrier. The hybrid Small Nucleolar RNA:ribozyme, designated a “snorbozyme,” is metabolically stable and cleaves a target U3 RNA with nearly 100% efficiency in vivo. This is the most efficient in vivo cleavage reported for a trans-acting ribozyme. A key advantage of the model substrate featured is that a stable, trimmed cleavage product accumulates. This property allows accurate kinetic measurements of authentic cleavage in vivo. The system offers new avenues for developing effective ribozymes for research and therapeutic applications.

  • Functional mapping of the U3 Small Nucleolar RNA from the yeast Saccharomyces cerevisiae.
    Molecular and cellular biology, 1998
    Co-Authors: Dmitry Samarsky, Maurille J. Fournier
    Abstract:

    The U3 Small Nucleolar RNA participates in early events of eukaryotic pre-rRNA cleavage and is essential for formation of 18S rRNA. Using an in vivo system, we have developed a functional map of the U3 Small Nucleolar RNA from Saccharomyces cerevisiae. The test strain features a galactose-dependent U3 gene in the chromosome and a plasmid-encoded allele with a unique hybridization tag. Effects of mutations on U3 production were analyzed by evaluating RNA levels in cells grown on galactose medium, and effects on U3 function were assessed by growing cells on glucose medium. The major findings are as follows: (i) boxes C′ and D and flanking helices are critical for U3 accumulation; (ii) boxes B and C are not essential for U3 production but are important for function, most likely due to binding of a trans-acting factor(s); (iii) the 5′ portion of U3 is required for function but not stability; and, (iv) strikingly, the nonconserved hairpins 2, 3, and 4, which account for 50% of the molecule, are not required for accumulation or function.

  • the rRNA processing function of the yeast u14 Small Nucleolar RNA can be rescued by a conserved RNA helicase like protein
    Molecular and Cellular Biology, 1997
    Co-Authors: W Q Liang, J A Clark, Maurille J. Fournier
    Abstract:

    The phylogenetically conserved U14 Small Nucleolar RNA is required for processing of rRNA, and this function involves base pairing with conserved complementary sequences in 18S RNA. With a view to identifying other important U14 interactions, a stem-loop domain required for activity of Saccharomyces cerevisiae U14 RNAs (the Y domain) was first subjected to detailed mutational analysis. The mapping results showed that most nucleotides of the Y domain can be replaced without affecting function, except for loop nucleotides conserved among five different yeast species. Defective variants were then used to identify both intragenic and extragenic suppressor mutations. All of the intragenic mutations mapped within six nucleotides of the primary mutation, suggesting that suppression involves a change in conformation and that the loop element is involved in an essential intermolecular interaction rather than intramolecular base pairing. A high-copy extragenic suppressor gene, designated DBP4 (DEAD box protein 4), encodes an essential, putative RNA helicase of the DEAD-DEXH box family. Suppression by DBP4 (initially CA4 [T.-H. Chang, J. Arenas, and J. Abelson, Proc. Natl. Acad. Sci. USA 87:1571-1575, 1990]) restores the level of 18S rRNA and is specific for the Y domain but is not allele specific. DBP4 is predicted to function either in assembly of the U14 Small Nucleolar RNP or, more likely, in its interaction with other components of the rRNA processing apparatus. Mediating the interaction of U14 with precursor 18S RNA is an especially attractive possibility.

David Tollervey - One of the best experts on this subject based on the ideXlab platform.

  • base pairing between u3 Small Nucleolar RNA and the 5 end of 18s rRNA is required for pre rRNA processing
    Molecular and Cellular Biology, 1999
    Co-Authors: Kishor Sharma, David Tollervey
    Abstract:

    The loop of a stem structure close to the 5′ end of the 18S rRNA is complementary to the box A region of the U3 Small Nucleolar RNA (snoRNA). Substitution of the 18S loop nucleotides inhibited pre-rRNA cleavage at site A1, the 5′ end of the 18S rRNA, and at site A2, located 1.9 kb away in inteRNAl transcribed spacer 1. This inhibition was largely suppressed by a compensatory mutation in U3, demonstrating functional base pairing. The U3–pre-rRNA base pairing is incompatible with the structure that forms in the mature 18S rRNA and may prevent premature folding of the pre-rRNA. In the Escherichia coli pre-rRNA the homologous region of the 16S rRNA is also sequestered, in that case by base pairing to the 5′ exteRNAl transcribed spacer (5′ ETS). Cleavage at site A0 in the yeast 5′ ETS strictly requires base pairing between U3 and a sequence within the 5′ ETS. In contrast, the U3-18S interaction is not required for A0 cleavage. U3 therefore carries out at least two functionally distinct base pair interactions with the pre-rRNA. The nucleotide at the site of A1 cleavage was shown to be specified by two distinct signals; one of these is the stem-loop structure within the 18S rRNA. However, in contrast to the efficiency of cleavage, the position of A1 cleavage is not dependent on the U3-loop interaction. We conclude that the 18S stem-loop structure is recognized at least twice during pre-rRNA processing.

  • Identification and functional analysis of a novel yeast Small Nucleolar RNA
    Nucleic acids research, 1993
    Co-Authors: Thomas Dandekar, David Tollervey
    Abstract:

    snR31 Is a RNA species of 225 nt. which has the tri­ methyl guanosine cap structure typical of Small nuclear RNAs (snRNAs) and yeast Small Nucleolar RNAs (snoRNAs), and Is associated with the Nucleolar proteins flbrillarln (NOP1) and GAR1. On sub-nuclear fractlonatlon, snR31 behaves like other snoRNAs, and Is enriched in a Nucleolar fraction. The SNR31 genomic locus is close to the SNR5 locus, which encodes another snoRNA. The two genes are divergently transcribed with 217 bp separating the transcription start sites. Disruption of the SNR31 gene does not detectably impair growth in a haploid strain. Analyses of pre-rRNA processing In wild-type and snr31strains shows some accumulation of the 35S primary transcript In the mutant, indicating a mild Impairment of the initial steps in pre-rRNA processing.

  • Yeast snR30 is a Small Nucleolar RNA required for 18S rRNA synthesis.
    Molecular and cellular biology, 1993
    Co-Authors: John P. Morrissey, David Tollervey
    Abstract:

    Subnuclear fractionation and coprecipitation by antibodies against the Nucleolar protein NOP1 demonstrate that the essential Saccharomyces cerevisiae RNA snR30 is localized to the nucleolus. By using aminomethyl trimethyl-psoralen, snR30 can be cross-linked in vivo to 35S pre-rRNA. To determine whether snR30 has a role in rRNA processing, a conditional allele was constructed by replacing the authentic SNR30 promoter with the GAL10 promoter. Repression of snR30 synthesis results in a rapid depletion of snR30 and a progressive increase in cell doubling time. rRNA processing is disrupted during the depletion of snR30; mature 18S rRNA and its 20S precursor underaccumulate, and an aberrant 23S pre-rRNA intermediate can be detected. Initial results indicate that this 23S pre-rRNA is the same as the species detected on depletion of the Small Nucleolar RNA-associated proteins NOP1 and GAR1 and in an snr10 mutant strain. It was found that the 3' end of 23S pre-rRNA is located in the 3' region of ITS1 between cleavage sites A2 and B1 and not, as previously suggested, at the B1 site, snR30 is the fourth Small Nucleolar RNA shown to play a role in rRNA processing.

Feng Jiang - One of the best experts on this subject based on the ideXlab platform.

  • genome wide Small Nucleolar RNA expression analysis of lung cancer by next generation deep sequencing
    International Journal of Cancer, 2015
    Co-Authors: Lu Gao, Kaiissar Mannoor, Maria A. Guarnera, Amol C Shetty, Min Zhan, Lingxiao Xing, Sanford A Stass, Feng Jiang
    Abstract:

    Abstract Emerging evidence indicates that Small Nucleolar RNAs (snoRNAs), a class of Small noncoding RNAs, may play important function in tumorigenesis. NonSmall-cell lung cancer (NSCLC) is the number one cancer killer for men and women. Systematically characterizing snoRNAs in NSCLC will develop biomarkers for its early detection and prognostication. We used next-generation deep sequencing to comprehensively characterize snoRNA profiles in 12 NSCLC tissues. We used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the findings in 40 surgical Stage I NSCLC specimens and 126 frozen NSCLC tissues of different stages. The 126 NSCLC tissues were divided into a training set and a testing set. Deep sequencing identified 458 snoRNAs, of which, 29 had a ≥3.0-fold expression level change in Stage I NSCLC tissues versus normal tissues. qRT-PCR analysis showed that 16 of 29 snoRNAs exhibited consistent changes with deep sequencing data. The 16 snoRNAs exhibited 0.75-0.94 area under receiver-operator characteristic curve values in distinguishing lung tumor from normal lung tissues (all ≤0.0001) with 70.0-95.0% sensitivity and 70.0-95.0% specificity. Six genes (snoRA47, snoRA68, snoRA78, snoRA21, snoRD28 and snoRD66) were identified whose expressions were associated with overall survival of the NSCLC patients. A prediction model consisting of three genes (snoRA47, snoRA68 and snoRA78) was developed in the training set of 77 cases, which could significantly predict overall survival of the NSCLC patients (p < 0.0001). The prognostic performance of the prediction model was confirmed in the testing set of 49 NSCLC patients. The identified snoRNA signatures may provide potential biomarkers for the early detection and prognostication of NSCLC.

  • Small Nucleolar RNA signatures of lung tumor-initiating cells
    Molecular cancer, 2014
    Co-Authors: Kaiissar Mannoor, Jipei Liao, Jun Shen, Zhenqiu Liu, Feng Jiang
    Abstract:

    Background Non-Small cell lung cancer (NSCLC) is the number one cancer killer. Tumor-initiating cells (TICs) are responsible for tumor progression and recurrence. Emerging evidences suggest that Small Nucleolar RNAs (snoRNAs) play malfunctioning roles in lung tumorigenesis. This study aims to determine if snoRNAs have important function in lung TICs by: 1) profiling and comparing snoRNA expression patterns in lung ALDH1+/- cells of 28 primary NSCLC tissues to identify new signatures of TICs; 2) determining prognostic significance of the snoRNA signatures by analyzing the expression in 82 NSCLC tissues with different stages and histological types using quantitative PCR; 3) functionally investigating if the snoRNAs contribute to stemness of lung TICs using in vitro and in vivo assays.

  • Small Nucleolar RNA signatures as biomarkers for non-Small-cell lung cancer
    Molecular cancer, 2010
    Co-Authors: Jipei Liao, Yuping Mei, Jun Shen, Zhenqiu Liu, Maria A. Guarnera, Feng Jiang
    Abstract:

    Background Non-Small-cell lung cancer (NSCLC) is the leading cause of cancer death. Early detection of NSCLC will improve its outcome. The current techniques for NSCLC early detection are either invasive or have low accuracy. Molecular analyses of clinical specimens present promising diagnostic approaches. Non-coding RNAs (ncRNAs) play an important role in tumorigenesis and could be developed as biomarkers for cancer. Here we aimed to develop Small Nucleolar RNAs (snoRNAs), a common class of ncRNAs, as biomarkers for NSCLC early detection. The study comprised three phases: (1) profiling snoRNA signatures in 22 NSCLC tissues and matched noncancerous lung tissues by GeneChip Array, (2) validating expressions of the signatures by RT-qPCR in the tissues, and (3) evaluating plasma expressions of the snoRNAs in 37 NSCLC patients, 26 patients with chronic obstructive pulmonary disease (COPD), and 22 healthy subjects.

Susan A. Gerbi - One of the best experts on this subject based on the ideXlab platform.

  • u3 Small Nucleolar RNA is essential for cleavage at sites 1 2 and 3 in pre rRNA and determines which rRNA processing pathway is taken in xenopus oocytes
    Journal of Molecular Biology, 1999
    Co-Authors: Anton V. Borovjagin, Susan A. Gerbi
    Abstract:

    Abstract A molecular dissection of U3 Small Nucleolar RNA (snoRNA) was performed in vivo inXenopus oocytes and the effects on rRNA processing were analyzed. Oocyte injection of antisense oligonucleotides against parts of U3 snoRNA resulted in specific fragmentation of U3 by endogenous RNAse H. Fragmentation of U3 domain II correlated with a decrease in 20 S pre-rRNA and a concomitant increase in 36 S pre-rRNA, indicating reduced cleavage at site 3. Conversely, fragmentation of U3 domain I completely blocked 18 S rRNA formation, increased the 20 S rRNA precursor, and decreased 36 S pre-rRNA, indicating inhibition of cleavage at sites 1+2. rRNA processing defects at sites 1+2 or 3 after destruction of intact endogenous U3 snoRNA were rescued by injection of in vitro transcripts of U3 snoRNA or certain U3 fragments. Thus, cleavage at sites 1+2 and 3 is U3 snoRNA dependent. Moreover, U3 snoRNA has two functional modules: domain I for sites 1+2 cleavage and domain II for site 3 cleavage. The data suggest that whichever of these U3 domains acts first determines which rRNA processing pathway will be taken: cleavage first at site 3 of pre-rRNA leads to pathway A, whereas cleavage first at sites 1+2 leads to pathway B for rRNA processing. Predictions of this model were validated by rescue of site 3 cleavage by injection of just domain II after U3 depletion. Rescue of sites 1+2 cleavage required covalent continuity of domain I with the hinge region and non-covalent association with domain II. We could experimentally shift which rRNA processing pathway was taken by injecting fragments of U3 to compete with endogenous U3 snoRNA.

  • Nucleolar LOCALIZATION ELEMENTS OF XENOPUS LAEVIS U3 Small Nucleolar RNA
    Molecular biology of the cell, 1998
    Co-Authors: Thilo S. Lange, Michael Ezrokhi, Anton V. Borovjagin, Rafael Rivera-león, Melanie T. North, Susan A. Gerbi
    Abstract:

    The Nucleolar Localization Elements (NoLEs) of Xenopus laevis U3 Small Nucleolar RNA (snoRNA) have been defined. Fluorescein-labeled wild-type U3 snoRNA injected into Xenopus oocyte nuclei localized specifically to nucleoli as shown by fluorescence microscopy. Injection of mutated U3 snoRNA revealed that the 59 region containing Boxes A and A9, known to be important for rRNA processing, is not essential for Nucleolar localization. Nucleolar localization of U3 snoRNA was independent of the presence and nature of the 59 cap and the terminal stem. In contrast, Boxes C and D, common to the Box C/D snoRNA family, are critical elements for U3 localization. Mutation of the hinge region, Box B, or Box C9 led to reduced U3 Nucleolar localization. Results of competition experiments suggested that Boxes C and D act in a cooperative manner. It is proposed that Box B facilitates U3 snoRNA Nucleolar localization by the primary NoLEs (Boxes C and D), with the hinge region of U3 subsequently base pairing to the exteRNAl transcribed spacer of pre-rRNA, thus positioning U3 snoRNA for its roles in rRNA processing.

  • Small Nucleolar RNA
    Biochemistry and cell biology = Biochimie et biologie cellulaire, 1995
    Co-Authors: Susan A. Gerbi
    Abstract:

    A growing list of Small Nucleolar RNAs (snoRNAs) has been characterized in eukaryotes. They are transcribed by RNA polymerase II or III; some snoRNAs are encoded in the introns of other genes. The nonintronic polymerase II transcribed snoRNAs receive a trimethylguanosine cap, probably in the nucleus, and move to the nucleolus. snoRNAs are complexed with proteins, sometimes including fibrillarin. Localization and maintenance in the nucleolus of some snoRNAs requires the presence of initial precursor rRNA (pre-rRNA). Many snoRNAs have conserved sequence boxes C and D and a 3′ terminal stem; the roles of these features are discussed. Functional assays done for a few snoRNAs indicate their roles in rRNA processing for cleavage of the exteRNAl and inteRNAl transcribed spacers (ETS and ITS). U3 is the most abundant snoRNA and is needed for cleavage of ETS1 and ITS1; experimental results on U3 binding sites in pre-rRNA are reviewed. 18S rRNA production also needs U14, U22, and snR30 snoRNAs, whereas U8 snoRNA is...