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Exon-intron boundary sequence of NOB1 gene. Intron and exon nucleotide sequences are shown in lower-case and upper- case letters, respectively. Bold lettering indicates donor and acceptor splice sites
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The yeast Nob1p (Nin one binding protein) gene is required for proteasome function and RNA metabolism. We report here the cloning and characterization of the human orthologue NOB1 gene and its products. The human NOB1 gene is composed of nine exons and eight introns and is localized on human chromosome 16q22.1. The NOB1 cDNA is 1749 bp long and con...
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Citations
... In the final steps of cytoplasmic maturation of the pre-40S, the 3ʹ end of the 20S rRNA is cleaved by nuclease Nob1 at cleavage site D to form 18S rRNA and further generating translationally capable 40S subunit [14][15][16][17]. Nob1 contains the PilT N-terminal (PIN) domain [14,16], which is common to exonuclease or endonuclease [18,19] and zinc ribbon domain [20][21][22]. PNO-1 (partner of Nob1p) is the interaction partner of the endonuclease Nob1; it regulates the enzymatic function of Nob1 and together with Nob1 mediates the cleavage of 20S rRNA into mature 18S rRNA [23]. ...
Background
Ribosome biogenesis is the process of assembling ribosome complexes that regulate cell proliferation and differentiation with potential regulatory effects on development. Many factors regulate ribosome biological processes. Nin one binding protein (Nob1) has received widespread attention as key genes regulating ribosome biogenesis—the 3ʹ end of the 20S rRNA is cleaved by Nob1 at cleavage site D to form 18S rRNA, generating translationally capable 40S subunit. As a ribosome biogenesis factor, Nob1 may regulate the development of organisms, but almost nothing is known about the function of Nob1 for any parasitic nematode. We explored the functional role of NOBP-1 (the homologous gene of Nob1) encoding gene from a parasitic nematode—Strongyloides stercoralis.
Methods
The full-length cDNA, gDNA and promoter region of Ss-nobp-1 was identified using protein BLAST in WormBase ParaSite according to the Caenorhabditis elegans NOBP-1 sequence to analyze the gene structure. RNA sequencing (RNA-seq) data in wormbase were retrieved and analyzed to assess the transcript abundance of Ss-nobp-1 in seven developmental stages of S. stercoralis. The standard method for gonadal microinjection of constructs was carried out to determine the anatomic expression patterns of Ss-nobp-1. The interaction between Ss-NOBP-1 and partner of NOBP-1 (Ss-PNO-1) was assessed by yeast two-hybridization and bimolecular fluorescence complementarity (BiFC) experiments.
Results
The NOBP-1 encoding gene Ss-nopb-1 from the zoonotic parasite S. stercoralis has been isolated and characterized. The genomic DNA representing Ss-nobp-1 includes a 1599-bp coding region and encodes a protein comprising 403 amino acids (aa), which contains conserved PIN domain and zinc ribbon domain. RNA-seq analysis revealed that Ss-nobp-1 transcripts are present throughout the seven developmental stages in S. stercoralis and have higher transcription levels in iL3, L3 and P Female. Ss-nobp-1 is expressed mainly in the intestine of transgenic S. stercoralis larvae, and there is a direct interaction between Ss-NOBP-1 and Ss-PNO-1.
Conclusions
Collectively, Ss-NOBP-1 has a potential role in embryo formation and the infective process, and findings from this study provide a sound foundation for investigating its function during the development of parasitic nematode.
Graphical Abstract
... The NIN1 (RPN12) homolog of binding protein 1 (NOB1) is located on chromosome 16q22.1 and consists of nine exons and eight introns [309]. The RNA substrate containing the D-site of proribosomal RNA is efficiently cleaved by NOB1 in a manganese-dependent manner, regulating protease function and RNA metabolism. ...
The major challenges in Osteosarcoma (OS) therapy are its heterogeneity and drug resistance. The development of new therapeutic approaches to overcome the major growth mechanisms of OS is urgently needed. The search for specific molecular targets and promising innovative approaches in OS therapy, including drug delivery methods, is an urgent problem. Modern regenerative medicine focuses on harnessing the potential of mesenchymal stem cells (MSCs) because they have low immunogenicity. MSCs are important cells that have received considerable attention in cancer research. Currently, new cell-based methods for using MSCs in medicine are being actively investigated and tested, especially as carriers for chemotherapeutics, nanoparticles, and photosensitizers. However, despite the inexhaustible regenerative potential and known anticancer properties of MSCs, they may trigger the development and progression of bone tumors. A better understanding of the complex cellular and molecular mechanisms of OS pathogenesis is essential to identify novel molecular effectors involved in oncogenesis. The current review focuses on signaling pathways and miRNAs involved in the development of OS and describes the role of MSCs in oncogenesis and their potential for antitumor cell-based therapy.
... The NIN1/RPN12 binding protein 1 homolog (NOB1) gene encodes the NOB1 protein containing a PilT amino terminus (PIN) domain and a C terminal zinc ribbon domain [8]. The human NOB1 gene is composed of nine exons and eight introns and is localized on human chromosome 16q22.1 [9]. Nob1 is involved in pre-rRNA processing. ...
MicroRNAs (miRNAs) play crucial roles in cancer progression. Our previous study demonstrated that NIN1/RPN12 binding protein 1 homolog (NOB1) was a functional regulator in the progression of ovarian cancer (OC). However, the role of miRNA-612 (miR-612) in OC has not been elucidated. In this study, we aimed to investigate the regulatory mechanism of NOB1 targeting miRNA, miR-612, in OC tumorigenicity. The miR-612 expression was down-regulated in OC patient tissues and four OC cell lines (Caov3, A2780, SKOV3 and OVCAR3). The miR-612 level was negatively correlated with NOB1 expression, and dual-luciferase reporter assay indicated that miR-612 suppressed NOB1 expression by targeting the 3'UTR of NOB1 transcript. Up-regulation of miR-612 mediated by lentiviral transduction suppressed cell proliferation, colony formation, migration, invasion, and induced apoptosis in OC cell lines. In addition, miR-612 overexpression inhibited tumor growth of OC in vivo by sequestering NOB1 expression. In conclusion, our results suggested that miR-612 directly targeted NOB1 to suppress OC progression. Therefore, the miR-612-NOB1 axis could serve as therapeutic targets for OC.
... ProSA was used for overall perspective and checking the model structural quality for potential errors; the program shows a plot of its residue energies and Z-scores, which determine the overall quality of the model (22). TM align software was used for 3-D structure alignment of IR protein for different species and RMSD prediction to generate the structural differentiation (23). The solvent accessibility surface area of the IR genes was generated by using NetSurfP server (http://www.cbs.dtu.dk/services/ ...
Retinoic acid inducible gene I (RIG-I) is associated to the DExD/H box RNA helicases. It is a pattern recognition receptor (PRR), playing a crucial role in the system and is a germ line encoded host sensor to perceive pathogen-associated molecular patterns (PAMPs). So far, reports are available for the role of RIG-I in antiviral immunity. This is the first report in which we have documented the role of RIG-I in parasitic immunity. Haemonchus contortus is a deadly parasite affecting the sheep industry, which has a tremendous economic importance, and the parasite is reported to be prevalent in the hot and humid agroclimatic region. We characterize the RIG-I gene in sheep (Ovis aries) and identify the important domains or binding sites with Haemonchus contortus through in silico studies. Differential mRNA expression analysis reveals upregulation of the RIG-I gene in the abomasum of infected sheep compared with that of healthy sheep, further confirming the findings. Thus, it is evident that, in infected sheep, expression of RIG-I is triggered for binding to more pathogens (Haemonchus contortus). Genetically similar studies with humans and other livestock species were conducted to reveal that sheep may be efficiently using a model organism for studying the role of RIG-I in antiparasitic immunity in humans.
... The ProSA was used for overall prospective and checking the model structural quality with potential errors and program shows a plot of its residue energies and Z-scores which determine overall quality of model 18 . TM align software was used for 3 D structure alignment of IR protein for different species and RMSD prediction to generate the structural differentiation 19 . The solvent accessibility surface area of the IR genes was generated by using NetSurfP server (http://www.cbs.dtu.dk/services/NetSurfP/) ...
RIG-I is associated to the DExD/H box RNA Helicases. It is a Pattern Recognition Receptor (PRR), playing a crucial role in the system and is a germ line encoded host sensor to perceive Pathogen Associated Molecular Patterns or PAMPs. So far reports were available for the role of RIG-I in antiviral immunity. This is the first report we have documented the role of RIG-I in parasitic immunity. Haemonchus contortus is a deadly parasite affecting sheep industry which has a tremendous economic importance and the parasite reported to be prevalent in the hot and humid agroclimatic region. We had characterized RIG-I gene in sheep (Ovis aries) and identified the important domains or binding site with Haemonchus contortus through in silico studies. Differential mRNA expression analysis revealed upregulation of RIG-I gene in abomassum of infected sheep compared to that of healthy sheep, further confirming the findings. Thus it is evident that in infected sheep, expression of RIG-I is triggered for binding to more pathogen (Haemonchus contortus). Genetic similar studies with human and other livestock species were conducted to reveal that sheep may be efficiently used a model organism for studying the role of RIG-I in antiparasitic immunity of human.
... Due to the incurable nature and the low survival rate, a huge attention has been focused on lung cancer to nd early detection strategies [9]. NIN1/RPN12 binding protein 1 homolog (NOB1) is located in chromosome 16q22.1 [10]. This gene was rstly identi ed in Saccharomyces cerevisiae, encodes the essential protein Nin one binding protein (NOB1p) [11]. ...
... And it may participate in occurrence and development of the various tumors by regulating the gene transcription. NOB1 is mainly expressed in the liver, lung and spleen, and downregulated in kidney, prostate, colon and ovarian tissues [10]. Increasing studies indicated that NOB1 has extensive biological functions, for example, it participated in the synthesis and assembling of 26s proteasome and ribosome, regulating cell cycle through the UPP pathway. ...
Background: NIN1/RPN12 binding protein 1 homolog (NOB1) gene was reported to play a key role in the oncogenesis and prognosis of carcinomas. The aim of the present study was to investigate the expression of NOB1 and its clinical significance in lung cancer, and further explore the diagnostic value of NOB1 in lung cancer patients.
Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to characterize the expression of NOB1 in 97 lung cancer patients and 55 healthy controls. The associations of NOB1 mRNA expression with clinicopathological factors of lung cancer patients were analyzed by Chi-square test. The receiver operating characteristics (ROC) curve was used to evaluate the diagnostic value of NOB1 in lung cancer.
Results: The expression levels of NOB1 mRNA in lung cancer samples were significantly up-regulated compared with healthy controls (P<0.001). And the NOB1 expression was significant correlated with differentiation (P=0.005) and invasion depth (P=0.008). No associations were found between NOB1 expression and other factors (All P>0.05). ROC curve revealed that the area under ROC curve (AUC) was 0.885, with a sensitivity of 76.3% and a specificity of 89.1%. And the cutoff value of NOB1 was 2.225.
Conclusion: NOB1 is a sensitive and specific diagnostic marker for lung cancer, and provide a new therapeutic target for lung cancer treatment.
... However, in osteosarcoma, there are little papers which study on metastasis of miR-363; therefore, we now investigate whether miR-363 suppressed cell migration, invasion, and EMT in osteosarcoma. NIN1 (RPN12) binding protein 1 homolog (NOB1) is located on chromosome 16q22.1 and consists of nine exons and eight introns [16]. The RNA substrate containing the D site of pro-ribosomal RNA is efficiently cleaved by NOB1 in a manganese-dependent manner, thereby regulating protease function and RNA metabolism [17]. ...
... NOB1 could cleave RNA substrate that contains the D site of pro-ribosomal RNA, thereby regulating protease functions and RNA metabolism [16]. NOB1 acted as an oncogene and was upregulated in a variety of cancers that include cervical cancer, gastric cancer, epithelial ovarian cancer, and non-small cell lung cancer [18][19][20][21]. ...
Background:
Osteosarcoma (OS) is a primary malignant bone tumor with a high rate of metastasis and a short 5-year survival rate. MiR-363 was downregulated in a variety of tumors and played a role in suppressing tumors. However, the roles of miR-363 in osteosarcoma remain unknown; thus, the purpose of this study was to explore the functions of miR-363 in osteosarcoma.
Methods:
CCK-8 and transwell assays were performed to evaluate the proliferation, migration, and invasion abilities of MG63 cells. The epithelial-mesenchymal transition (EMT) and apoptosis-associated proteins were measured by using Western blot assay. Luciferase reporter assay was utilized to verify whether miR-363 directly bound to the 3'-UTR of NOB1 mRNA.
Results:
MiR-363 was downregulated while NOB1 was upregulated in osteosarcoma clinical tissue specimens and cell lines as compared with the adjacent normal tissue specimens and normal cell line. The miR-363 is reversely correlated with the expression of NOB1 in osteosarcoma tissues. Overexpression of miR-363 suppressed the ability of cell migration, invasion, and EMT, whereas low expression of miR-363 promoted this ability. In addition, miR-363 inhibited osteosarcoma proliferation both in vitro and in vivo and inhibited the apoptosis in MG63 cells. Interference of NOB1 could inhibit the migration, invasion, and EMT of osteosarcoma cell line MG63. NOB1 was verified to be a direct target of miR-363 and its expression was mediated by miR-363. Re-expression of NOB1 could partially reverse the inhibitory effect of miR-363 on cell migration and invasion. In addition, low expression of miR-363 or overexpression of NOB1 predicted poor prognosis of osteosarcoma patients.
Conclusion:
MiR-363 inhibited osteosarcoma the proliferation, migration, invasion, and EMT and induced the apoptosis by directly targeting NOB1 in MG63 cells. The newly identified miR-363/NOB1 axis provides novel insights into the pathogenesis of osteosarcoma.
... Ce mécanisme est conservé chez la levure mais aussi les eucaryotes supérieurs comme l'homme et enfin chez les archaebactéries. Nob1 a été initialement isolée chez la levure par des expériences de criblage en double hybride avec la protéine Rnp12 qui est une composante de la machinerie de dégradation (protéasome) (Zhang et al., 2005). ...
... Chez un individu adulte, cette protéine est exprimée dans tous les types cellulaires mais en plus grande quantité dans les tissus pulmonaires, le foie et la rate. Nob1 est localisée dans le noyau et dans le cytoplasme (Zhang et al., 2005). C'est une protéine de 46 kDa et son ORF est localisée au niveau du chromosome 16q22.1 qui est constituée de 9 exons et de 8 introns. ...
Les ribosomes sont des complexes nucléoproétiques responsables de la traduction. Chez les eucaryotes, la biogenèse du ribosome est un processus complexe très régulé qui fait intervenir un nombre important de facteurs d’assemblages (~200). La construction d’un ribosome est initiée dans le nucléole puis continue dans le nucléoplasme et se termine dans le cytoplasme. La maturation cytoplasmique de la petite sous-unité ribosomale implique la dissociation séquentielle des facteurs d’assemblage tardifs et la maturation finale de l’ARNr 18S. Ce processus est catalysé par l’endonucléase Nob1 qui assure la coupure de l’extrémité 3’ du précurseur de l’ARNr 18S (pré-18S) aboutissant à sa forme mature. Ce mécanisme est coordonné par la protéine Pno1 qui est le partenaire de Nob1. Des informations détaillées sur l’architecture des particules pré-ribosomiques nous ont permis de mieux comprendre les différents intermédiaires de la biogenèse. Cependant, certains aspects fonctionnels comme la conformation adoptée par Nob1 pour assurer la coupure du site D du pre-18S reste encore flou. L’objectif de mon travail a été de mieux comprendre les aspects très tardifs de la maturation cytoplasmique du ribosome. Pour ce faire, nous avons redéfini l’organisation modulaire de l’endonucléase Nob1 chez les eucaryotes pour ensuite étudier son mode d’interaction avec son partenaire Pno1. Des tests fonctionnels in vitro ont été effectués pour étudier le rôle de Pno1 dans la régulation de la coupure par Nob1.Nos résultats nous ont permis de montrer que le domaine catalytique de Nob1 adopte une conformation atypique. En effet le domaine PIN est composé de deux fragments (res 1-104 and 230-255) séparé par une boucle interne qui est importante pour la reconnaissance avec son partenaire Pno1. Nos études nous ont également montré que Pno1 inhibe l’activité de Nob1 probablement en reconnaissant directement l’ARNr substrat, masquant ainsi le site de coupure de l’endonucléase. Ces résultats sont complémentaires et cohérents avec les données structurales de cryo-EM de la particule pré-40S humaine récemment publiées. En effet, Nob1 est dans une conformation incapable de couper le pré-ARNr puisque son domaine catalytique se retrouve à une distance d’environ 30Å de son ARN substrat. Ce phénomène implique donc des changements de conformations ou encore la nécessité de protéine accessoire pour déplacer certains facteurs. La protéine Cinap est impliqué dans la maturation de l’ARNr 18S. Nos études d’interaction avec les protéines localisées au niveau de la plateforme (à savoir RPS14, RPS26, le complexe Nob1/Pno1) ont permis de montrer que Cinap pouvait former un complexe tripartite avec l’endonucléase Nob1 et son partenaire Pno1. De plus, Cinap est capable de reconnaitre RPS26 dans un complexe RPS14-dépendant. Il est important de noter que RPS26 est un composant de la petite sous-unité qui remplace Pno1 dans le ribosome mature. De ce fait le recrutement de RPS26 au sein du pré-ribosome nécessite la dissociation de Pno1 et cet échange serait assurée par Cinap. Sur la base des travaux effectués, nous pouvons proposer un modèle de maturation où la formation du complexe Cinap/Pno1 induirait un changement de conformation permettant à Nob1 de reconnaitre son substrat et donc de catalyser la coupure du site D qui aboutit à la maturation de l’ARNr 18S et donc à la production de la sous-unité 40S mature.
... Structural bioinformatics is a branch of bioinformatics that focuses on the prediction of macromolecular structures, such as the structure of three-dimensional (3D) proteins (Zhang et al., 2005).One of the main questions in the problem of protein structure prediction is the challenge of understanding how the primary protein structure information is translated into a 3D structure and how to use this information for the development of prediction of the 3D structure (Creighton, 1990). ...
In Morocco, the epidemiological situation of infectious bronchitis virus (IBV) is very complex, because of the antigenic diversity associated with the emergence of new serotypes/genotypes and variants. The IBV strains circulating in poultry farms are serotypes/genotypes Italy02 and Massachussetts (Mass) identified during 2010-2014.
The appearance of these variants hinders the prophylactic strategy carried out by the breeders of the Moroccan poultry farm. To solve this problem we have opted for the rational design of candidate vaccines in order to study the structure of the three-dimensional (3D) S1 spicule protein of serotype Italy02 and Mass H120, through molecular modeling, using the I-Tasser server, then the COACH, and another Meta server to determine and predict the common immunogenic active sites between these two IBV strains circulating in Morocco.
The obtained results showed that the two strains studied had identical spatial conformation of the S1 protein structure with a similarity percentage of 81% and an average stability of the modeled sequences. Thus, both serotypes share active antigenic sites common in the hypervariable region, located at residues 229, 230, 232, 233 and 235, with a magnesium molecule association around the Alanine 280 region responsible for stimulating immunogenicity. The quality of the 3D conformation, the stability and the percentage make it possible to have accessibility to the common predicted neutralizing epitopes.
Based on these data, we can conclude that, it is highly probable that the H120 vaccine strain confers cross-protection against a challenge with new strains Italy02 circulating in Morocco.
Keys words: Infectious bronchitis virus, vaccine, modellling, epitope, cellular response
... The human NOB1 gene, which comprises nine exons and eight introns, is located on human chromosome 16q22.1; NOB1 encodes a 50-kDa protein, which comprises a PilT amino terminus domain and a zinc ribbon domain, and is predominantly expressed in the liver, lung and spleen (26). NOB1 functions as an oncogene, which is overexpressed and has important roles in various types of human cancer, including ovarian cancer (27), hepatocellular carcinoma (28), breast cancer (29), glioma (30), thyroid carcinoma (31) and prostate cancer (32). ...
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-associated mortality worldwide. Right open reading frame kinase 2 (RIOK2) and nin one binding protein (NOB1) are important accessory factors in ribosome assembly. In our previous study, RIOK2 and NOB1 were revealed to be highly expressed in NSCLC, and were associated with the clinicopathological characteristics of patients with NSCLC, i.e. TNM clinical stage, lymph node metastasis and differentiation. In addition, RIOK2 expression was correlated with NOB1. To further explore the mechanism and the RIOK2 and NOB1 signaling pathway, microRNA (miR) regulation was analyzed. The tumor suppressor miR‑145 has been reported to be lowly expressed in numerous types of human cancer; in the present study, the expression levels of miR‑145 were decreased in patients with NSCLC. Furthermore, RIOK2 and NOB1 were predicted to be the direct targets of miR‑145 using bioinformatics software; this was further validated using a dual luciferase reporter assay. In addition, the protein expression levels of RIOK2 and NOB1 were inhibited in response to miR‑145 overexpression, thus resulting in the suppression of cell viability, migration and invasion. These results suggested that RIOK2 and NOB1 may be potential targets in the treatment of NSCLC, and miR‑145 may be considered a therapeutic inhibitor of both genes.
