Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ZFAS1 promotes rRNA 2’O-methylationin by recruiting NOP58 contributes to colorectal cancer progression

ABSTRACT: Increasing evidence suggested that small nucleolar RNAs (snoRNAs) and long non-coding RNAs (LncRNAs) were master regulators of gene regulation at epigenetic modification level, however, the underlying mechanism in colorectal cancer (CRC) have not been investigated. To demonstrate the involvement of LncRNA and snoRNAs in 2’-O-methylation (Me) in tumorigenesis, we develop the LncRNAs-snoRNAs microarray of paired CRC tissues, and found an unrecognized ZFAS1-NOP58- SNORD12C/78 signaling axis in CRC tumorigenesis through recognizing the consensus AAGA motif of ZFAS1 which directly binds to NOP58 protein, and accelerating the snoRNPs assemble for further guiding 2’-O-Me of 28S rRNA. Strikingly, overexpression SNORD12C/78 induces 2’-O-Me modification upon ZFAS1, and affects RNA stability and translation activity of their downstream targets (e.g., EIF4A3,LMAC2, etc.), thereby promoted CRC cell proliferation, invasion and inhibited apoptosis in vitro and in vivo. Thus, these results sheds new light on our understanding of lncRNAs-snoRNPs mediated rRNA 2'-O-methylations in CRC tumorigenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE137511 | GEO | 2020/03/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

RNA helicase-mediated regulation of snoRNP dynamics on pre-ribosomes and rRNA 2’-O-methylation

Project description:RNA helicases play important roles in diverse aspects of RNA metabolism through their functions in remodelling ribonucleoprotein complexes (RNPs), such as pre-ribosomes. Here, we show that the DEAD box helicase Dbp3 is required for efficient processing of the U18 and U24 intron-encoded snoRNAs and 2'-O-methylation of various sites within the 25S ribosomal RNA (rRNA) sequence. Furthermore, numerous box C/D snoRNPs accumulate on pre-ribosomes in the absence of Dbp3. Many snoRNAs guiding Dbp3-dependent rRNA modifications have overlapping pre-rRNA basepairing sites and therefore form mutually exclusive interactions with pre-ribosomes. Analysis of the distribution of these snoRNAs between pre-ribosome-associated and 'free' pools demonstrated that many are almost exclusively associated with pre-ribosomal complexes. Our data suggest that retention of such snoRNPs on pre-ribosomes when Dbp3 is lacking may impede rRNA 2'-O-methylation by reducing the recycling efficiency of snoRNPs and by inhibiting snoRNP access to proximal target sites. The observation of substoichiometric rRNA modification at adjacent sites suggests that the snoRNPs guiding such modifications likely interact stochastically rather than hierarchically with their pre-rRNA target sites. Together, our data provide new insights into the dynamics of snoRNPs on pre-ribosomal complexes and the remodelling events occurring during the early stages of ribosome assembly.

2021-03-18 | GSE155720 | GEO

ZFAS1 promotes rRNA 2’O-methylationin by recruiting NOP58 contributes to colorectal cancer progression

Project description:ZFAS1 promotes rRNA 2’O-methylationin by recruiting NOP58 contributes to colorectal cancer progression

| PRJNA565758 | ENA

Translated Long Non-Coding Ribonucleic Acid ZFAS1 Promotes Cancer Cell Migration by Elevating Reactive Oxygen Species Production in Hepatocellular Carcinoma

Project description:Micropeptides (≤100 amino acids) are essential regulators of physiological and pathological processes, which can be encoded by small open reading frames (smORFs) derived from long non-coding RNAs (lncRNAs). Recently, lncRNA-encoded micropeptides have been shown to have essential roles in tumorigenesis. Since translated smORF identification remains technically challenging, little is known of their pathological functions in cancer. Therefore, we created classifiers to identify translated smORFs derived from lncRNAs based on ribosome-protected fragment sequencing and machine learning methods. In total, 537 putative translated smORFs were identified and the coding potential of five smORFs was experimentally validated via green fluorescent protein-tagged protein generation and mass spectrometry. After analyzing 11 lncRNA expression profiles of seven cancer types, we identified one validated translated lncRNA, ZFAS1, which was significantly up-regulated in hepatocellular carcinoma (HCC). Functional studies revealed that ZFAS1 can promote cancer cell migration by elevating intracellular reactive oxygen species production by inhibiting nicotinamide adenine dinucleotide dehydrogenase expression, indicating that translated ZFAS1 may be an essential oncogene in the progression of HCC. In this study, we systematically identified translated smORFs derived from lncRNAs and explored their potential pathological functions in cancer to improve our comprehensive understanding of the building blocks of living systems

2020-09-22 | GSE104226 | GEO

High-throughput sequencing approach for the identification of lncRNA biomarkers in hepatocellular carcinoma and reveal the effect of ZFAS1 on hepatocellular carcinoma progression（lncRNA and mRNA）

Project description:The aim of this study was to screen abnormal lncRNAs in the progression of hepatocellular carcinoma through high-throughput sequencing, and to screen the biomarkers for prognosis and diagnosis of hepatocellular carcinoma. Transcriptome analysis of 6 samples was completed in this project. A total of 93.581 Gb Clean Data (sequencing Data after quality control) was obtained. The average amount of Clean Data of each sample was 15.597 Gb. The Q30 base percentage was above 93.69 % and GC content was between 44.95% and 50.05%. In conclusion, sequencing analysis provided a landscape for abnormal regulation of lncRNAs, and screened out a significantly different lncRNAs ZFAS1. ZFAS1were found to be overexpressed in hepatocellular carcinoma tissues and correlated with malignant status and prognosis of hepatocellular carcinoma patients, and ZFAS1 silencing inhibited proliferation, migration and invasion of SK-Hep1 cells. The overexpression of miR-582-3p can eliminate the inhibitory effect of ZFAS1 silencing on SK-Hep1 cells, which may be valuable for the diagnosis and treatment of hepatocellular carcinoma. ZFAS1 may be a new potential biomarker for liver cancer. Further studies on the regulatory process of ZFAS1/miR-582-3p will help us to understand the mechanism of the occurrence and development of liver cancer

2021-10-16 | GSE185799 | GEO

NOPCHAP1 is a PAQosome cofactor that helps loading NOP58 on RUVBL1/2 during box C/D snoRNP biogenesis

Project description:The PAQosome is a large complex composed of the HSP90/R2TP chaperone and a prefoldin-like module. It promotes the biogenesis of cellular machineries but it is unclear how it discriminates closely related client proteins. Among the main PAQosome clients are C/D snoRNPs and in particular their core protein NOP58. Using NOP58 mutants and proteomic experiments, we identify different assembly intermediates and show that C12ORF45, which we rename NOPCHAP1, acts as a bridge between NOP58 and PAQosome. NOPCHAP1 makes direct physical interactions with the CC-NOP domain of NOP58 and domain II of RUVBL1/RUVBL2 AAA+ ATPases. Interestingly, NOPCHAP1 interaction with RuvBL1/2 is disrupted upon ATP binding. Moreover, while it robustly binds both yeast and human NOP58, it makes little interactions with NOP56 and PRPF31, two other closely related CC-NOP proteins. Expression of NOP58, but not NOP56 or PRPF31, is decreased in NOPCHAP1 KO cells. We propose that NOPCHAP1 is a client-loading PAQosome cofactor that selects NOP58 to promote box C/D snoRNP assembly.

2020-12-11 | GSE161155 | GEO

lncRNA-ZFAS1, an emerging gate-keeper in DNA damage-dependent transcriptional regulation [ZFAS1-mRNA-seq]

Project description:The hereditary information encoded in DNA sequence is intrinsically susceptible to alterations, being continually threatened by a variety of genotoxic perturbations. To safeguard the stability of the genome, eukaryotic cells have evolved a set of sophisticated surveillance system that controls several aspects of the cellular response, including the detection of DNA lesions, a temporary cell cycle arrest, regulation of transcription, and the repair of the damaged DNA. However, it is still poorly understood how the DNA damage checkpoints and stalled RNAPII molecules convert a very limited amount of molecular-level information (even a single DNA lesion) in the context of an otherwise genome into regulation that halts and resumes the cell-cycle engine in a coordinated way. In this study, we reveal a map of extensive lncRNA transcription during DDR by using synchronized cells, leading to the unexpected identification of a poorly characterized mammalian lncRNA-ZFAS1. We describe that ZFAS1 functions as a key player of cellular response to DNA damage in both human and rodent cells by fine tuning RNAPII kinetics, suggesting a lncRNA-dependent transcriptional regulatory axis that maintains genomic stability upon DNA damage in mammalian cells.

2023-08-03 | GSE239615 | GEO

lncRNA-ZFAS1, an emerging gate-keeper in DNA damage-dependent transcriptional regulation [ZFAS1 ChIRP-seq]

2023-08-03 | GSE239614 | GEO

Next generation sequencing identifies discrete classes of box C/D snoRNAs featuring different ends and RNA binding protein dependency

Project description:The paired-end next-generation sequencing of all small RNAs of less than 200 nucleotides in length from four different human cell lines (SKOV3ip1, MCF-7, BJ-Tielf, INOF) allowed us to determine the exact sequence(s) and variations of human box C/D snoRNAs (small nucleolar RNAs), revealing processing patterns of this class of molecules. Two distinct groups of box C/D snoRNAs were identified based on the position of their ends with respect to their characteristic boxes and the terminal base pairing potential. Short box C/D snoRNAs start sharply 4 or 5 nucleotides upstream of their box C and end 2 or 3 nucleotides downstream of their box D. In contrast, long box C/D snoRNAs start 5 or 6 nucleotides upstream of their box C and end 4 or 5 nucleotides downstream of their box D, increasing the likelihood of formation of a k-turn between their boxes C and D. Sequencing of SKOV3ip1 cells following the depletions of NOP58, a core box C/D snoRNA-binding protein and of RBFOX2, a splicing factor, shows that the short box C/D snoRNA forms are significantly more affected by the depletion of RBFOX2 while the long snoRNA forms, which display more canonical box C/D snoRNA features, are significantly more affected by the depletion of NOP58. Together the data suggest that box C/D snoRNAs are divided into at least two groups of RNA with distinct maturation and functional preferences. Small RNAs (<200 nucleotides) were isolated from different human cell lines that were either untreated or depleted of NOP58 or RBFOX2 using specific siRNAs. The resulting libraries were multiplexed and paired-end sequenced using Illumina HiSeq.

2014-07-01 | E-GEOD-55946 | biostudies-arrayexpress

Interactome of Prpf31 WT vs KA_AR mutant

Project description:The PAQosome is composed of the HSP90/R2TP chaperone and a prefoldin-like module. It promotes the biogenesis of cellular machineries but it is unclear how it discriminates closely related client proteins. Among the main PAQosome clients are C/D snoRNPs and in particular their core protein NOP58. Using NOP58 mutants and proteomic experiments, we identify different assembly intermediates and show that C12ORF45, which we rename NOPCHAP1, acts as a bridge between NOP58 and PAQosome. NOPCHAP1 makes direct physical interactions with the CC-NOP domain of NOP58 and the RUVBL1/RUVBL2 AAA+ ATPases. Interestingly, NOPCHAP1 binds several RUVBL1/2 mutants except those unable to hydrolyze ATP. Moreover, while it robustly binds both yeast and human NOP58, it makes only weak interactions with NOP56 and PRPF31, two other closely related CC-NOP proteins. Transient expression of NOP58, but not NOP56 or PRPF31, is decreased in NOPCHAP1 KO cells. We propose that NOPCHAP1 is a client-loading PAQosome cofactor that select NOP58 to promote box C/D snoRNP assembly.

2020-12-14 | PXD019416 | Pride

Interactome of NOP58 WT vs KA_AR mutant

2020-12-14 | PXD019415 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data