• BMB Reports
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• 제55권11호
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• pp.535-540
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• 2022

Ribosomes, acting as the cellular factories for protein production, are essential for all living organisms. Ribosomes are composed of both proteins and RNAs and are established through the coordination of several steps, including transcription, maturation of ribosomal RNA (rRNA), and assembly of ribosomal proteins. In particular, diverse factors required for ribosome biogenesis, such as transcription factors, small nucleolar RNA (snoRNA)-associated proteins, and assembly factors, are tightly regulated by various post-translational modifications. Among these modifications, small ubiquitin-related modifier (SUMO) targets lots of proteins required for gene expression of ribosomal proteins, rRNA, and snoRNAs, rRNA processing, and ribosome assembly. The tight control of SUMOylation affects functions and locations of substrates. This review summarizes current studies and recent progress of SUMOylation-mediated regulation of ribosome biogenesis.

• 생명과학회지
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• 제24권8호
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• pp.915-926
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• 2014

리보솜은 mRNA상의 유전정보를 단백질로 번역하는 세포에 필수적인 거대복합체이다. 이러한 리보솜은 리보 핵산단백질 복합체로, rRNA와 리보솜 단백질로 이루어져있다. 리보솜 조립과정은 리보솜 단백질 이외에도 많은 조립인자들이 각 구성요소의 조립을 도움으로써 이루어진다. 세포 내 리보솜 조립과정에 참여하는 조립인자들로 GTPase, ATPase, 샤페론, RNA helicase, 수식효소 등 다양한 단백질들이 알려졌다. 리보솜 조립과정 중 이러한 조립인자들은 리보솜 단백질 또는 rRNA의 수식에 참여하거나, 리보솜 단백질들과 rRNA의 조립 등을 돕는다. 이러한 리보솜 조립인자들에 관한 유전학적, 구조적, 생화학적 실험결과들이 많이 존재하지만 정확한 리보솜 조립과정과 이러한 조립인자들의 역할에 대해서는 아직 밝혀지지 않았다. 현재까지의 연구결과를 바탕으로 E. coli의 리보솜 조립과정을 돕는 단백질들에 대하여 알아보고자 한다.

• BMB Reports
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• 제52권8호
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• pp.502-507
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• 2019

Translation is a costly, but inevitable, cell maintenance process. To reduce unnecessary ATP consumption in cells, a fine-tuning mechanism is needed for both ribosome biogenesis and translation. Previous studies have suggested that the ribosome functions as a hub for many cellular signals such as ribotoxic stress response, mammalian target of rapamycin (mTOR), and ribosomal S6 kinase (RSK) signaling. Therefore, we investigated the relationship between ribosomes and mitogen-activated protein kinase (MAPK) activation under ribotoxic stress conditions and found that the activation of c-Jun N-terminal kinases (JNKs) was suppressed by ribosomal protein knockdown but that of p38 was not. In addition, we found that JNK activation is driven by the association of inactive JNK in the 80S monosomes rather than the polysomes. Overall, these data suggest that the activation of JNKs by ribotoxic stress is attributable to 80S monosomes. These 80S monosomes are active ribosomes that are ready to initiate protein translation, rather than polysomes that are already acting ribosomes involved in translation elongation.

• BMB Reports
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• 제57권5호
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• pp.232-237
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• 2024

This study investigated how adipose tissue-derived mesenchymal stem cells (AT-MSCs) respond to chondrogenic induction using droplet-based single-cell RNA sequencing (scRNA-seq). We analyzed 37,219 high-quality transcripts from control cells and cells induced for 1 week (1W) and 2 weeks (2W). Four distinct cell clusters (0-3), undetectable by bulk analysis, exhibited varying proportions. Cluster 1 dominated in control and 1W cells, whereas clusters (3, 2, and 0) exclusively dominated in control, 1W, and 2W cells, respectively. Furthermore, heterogeneous chondrogenic markers expression within clusters emerged. Gene ontology (GO) enrichment analysis of differentially expressed genes unveiled cluster-specific variations in key biological processes (BP): (1) Cluster 1 exhibited up-regulation of GO-BP terms related to ribosome biogenesis and translational control, crucial for maintaining stem cell properties and homeostasis; (2) Additionally, cluster 1 showed up-regulation of GO-BP terms associated with mitochondrial oxidative metabolism; (3) Cluster 3 displayed up-regulation of GO-BP terms related to cell proliferation; (4) Clusters 0 and 2 demonstrated similar up-regulation of GO-BP terms linked to collagen fibril organization and supramolecular fiber organization. However, only cluster 0 showed a significant decrease in GO-BP terms related to ribosome production, implying a potential correlation between ribosome regulation and the differentiation stages of AT-MSCs. Overall, our findings highlight heterogeneous cell clusters with varying balances between proliferation and differentiation before, and after, chondrogenic stimulation. This provides enhanced insights into the single-cell dynamics of AT-MSCs during chondrogenic differentiation.

• BMB Reports
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• 제46권1호
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• pp.9-16
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• 2013

In mammalian cells, aberrant transcripts harboring a premature termination codon (PTC) can be generated by abnormal or inefficient biogenesis of mRNAs or by somatic mutation. Truncated polypeptides synthesized from these aberrant transcripts could be toxic to normal cellular functions. However, mammalian cells have evolved sophisticated mechanisms for monitoring the quality of mRNAs. The faulty transcripts harboring PTC are subject to nonsense-mediated mRNA decay (NMD), nonsense-mediated translational repression (NMTR), nonsense-associated alternative splicing (NAS), or nonsense-mediated transcriptional gene silencing (NMTGS). In this review, we briefly outline the molecular characteristics of each pathway and suggest mRNA quality control mechanisms as a means to regulate normal gene expression.

• Journal of Animal Science and Technology
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• 제64권4호
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• pp.752-769
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• 2022

Wheat gluten is an increasingly common ingredient in poultry diets but its impact on the small intestine in chicken is not fully understood. This study aimed to identify effects of high-gluten diets on chicken small intestines and the variation of their associated transcriptional responses by age. A total of 120 broilers (Ross Strain) were used to perform two animal experiments consisting of two gluten inclusion levels (0% or 25%) by bird's age (1 week or 4 weeks). Transcriptomics and histochemical techniques were employed to study the effect of gluten on their duodenal mucosa using randomly selected 12 broilers (3 chicks per group). A reduction in feed intake and body weight gain was found in the broilers fed a high-gluten containing diet at both ages. Histochemical photomicrographs showed a reduced villus height to crypt depth ratio in the duodenum of gluten-fed broilers at 1 week. We found mainly a significant effect on the gene expression of duodenal mucosa in gluten-fed broilers at 1 week (289 differentially expressed genes [DEGs]). Pathway analyses revealed that the significant DEGs were mainly involved in ribosome, oxidative phosphorylation, and peroxisome proliferator-activated receptor (PPAR) signaling pathways. These pathways are involved in ribosome protein biogenesis, oxidative phosphorylation and fatty acid metabolism, respectively. Our results suggest a pattern of differential gene expression in these pathways that can be linked to chronic inflammation, suppression of cell proliferation, cell cycle arrest and apoptosis. And via such a mode of action, high-gluten inclusion levels in poultry diets could lead to the observed retardation of villi development in the duodenal mucosa of young broiler chicken.

• 대한의생명과학회지
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• 제28권4호
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• pp.260-275
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• 2022

Sterile alpha motif (SAM) domains bind to various proteins, lipids, and RNAs. However, these domains have not yet been analyzed as prognostic biomarkers. In this study, SAM domain containing 13 (SAMD13), a member of the SAM domain, was evaluated to identify a novel prognostic biomarker in various human cancers, including hepatocellular carcinoma (HCC). Moreover, we identified a correlation between SAMD13 expression and immune cell infiltration in HCC. We performed bioinformatics analysis using online databases, such as Tumor Immune Estimation Resource, UALCAN, Kaplan-Meier plotter, LinkedOmics, and Gene Expression Profiling Interactive Analysis2. SAMD13 expression in HCC samples was significantly higher than that in normal liver tissue; additionally, SAMD13 was higher in primary tumors, various stages of cancer and grades of tumor, and status of nodal metastasis. Higher SAMD13 expression was also associated with poorer prognosis. SAMD13 expression positively correlated with CD8+ T cells, CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells. In the analysis of SAMD13 co-expression networks, positively related genes of SAMD13 were associated with a high hazard ratio in different types of cancer, including HCC. In biological function of SAMD13, SAMD13 mainly include spliceosome, ribosome biogenesis in eukaryote, ribosome, etc. These results suggest that SAMD13 may serve as a novel prognostic biomarker for HCC diagnosis and provide novel insights into tumor immunology in HCC.

• Clinical and Experimental Pediatrics
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• 제57권8호
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• pp.337-344
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• 2014

Inherited bone marrow failure syndrome (IBMFS) encompasses a heterogeneous and complex group of genetic disorders characterized by physical malformations, insufficient blood cell production, and increased risk of malignancies. They often have substantial phenotype overlap, and therefore, genotyping is often a critical means of establishing a diagnosis. Current advances in the field of IBMFSs have identified multiple genes associated with IBMFSs and their pathways: genes involved in ribosome biogenesis, such as those associated with Diamond-Blackfan anemia and Shwachman-Diamond syndrome; genes involved in telomere maintenance, such as dyskeratosis congenita genes; genes encoding neutrophil elastase or neutrophil adhesion and mobility associated with severe congenital neutropenia; and genes involved in DNA recombination repair, such as those associated with Fanconi anemia. Early and adequate genetic diagnosis is required for proper management and follow-up in clinical practice. Recent advances using new molecular technologies, including next generation sequencing (NGS), have helped identify new candidate genes associated with the development of bone marrow failure. Targeted NGS using panels of large numbers of genes is rapidly gaining potential for use as a cost-effective diagnostic tool for the identification of mutations in newly diagnosed patients. In this review, we have described recent insights into IBMFS and how they are advancing our understanding of the disease's pathophysiology; we have also discussed the possible implications they will have in clinical practice for Korean patients.

• The Plant Pathology Journal
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• 제30권3호
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• pp.236-244
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• 2014

The plant pathogen Fusarium graminearum causes Fusarium head blight in cereal crops and produces mycotoxins that are harmful to animals and humans. For the initiation and spread of disease, asexual and sexual reproduction is required. Therefore, studies on fungal reproduction contribute to the development of new methods to control and maintain the fungal population. Screening a previously generated transcription factor mutant collection, we identified one putative $C_2H_2$ zincfinger transcription factor, pcs1, which is required for both sexual and asexual reproduction. Deleting pcs1 in F. graminearum resulted in a dramatic reduction in conidial production and a complete loss of sexual reproduction. The pathways and gene ontology of pcs1-dependent genes from microarray experiments showed that several G-protein related pathways, oxidase activity, ribosome biogenesis, and RNA binding and processing were highly enriched, suggesting that pcs1 is involved in several different biological processes. Further, overexpression of pcs1 increased conidial production and resulted in earlier maturation of ascospores compared to the wild-type strain. Additionally, the vegetative growth of the overexpression mutants was decreased in nutrient-rich conditions but was not different from the wild-type strain in nutrient-poor conditions. Overall, we discovered that the pcs1 transcription factor positively regulates both conidiation and sexual reproduction and confers nutrient condition-dependent vegetative growth.

• Bulletin of the Korean Chemical Society
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• 제33권6호
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• pp.2005-2011
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• 2012

Nopp140 is a highly phosphorylated protein that resides in the nucleolus of mammalian cell and is involved in the biogenesis of the nucleolus. It interacts with a variety of proteins related to the synthesis and assembly of the ribosome. It also can bind to a ubiquitous protein kinase CK2 that mediates cell growth and prevents apoptosis. We found that Nopp140 is an intrinsically unfolded protein (IUP) lacking stable secondary structures over its entire sequence of 709 residues. We discovered that mitoxantrone, an anticancer agent, was able to enhance the interaction between Nopp140 and CK2 and maintain suppressed activity of CK2. Surface plasma resonance studies on different domains of Nopp140 show that the C-terminal region of Nopp140 is responsible for binding with mitoxantrone. Our results present an interesting example where a small chemical compound binds to an intrinsically unfolded protein (IUP) and enhances protein-protein interactions.