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Genome-wide in-locus epitope tagging of Arabidopsis proteins using prime editors. 利用素编辑器对拟南芥蛋白质进行全基因组内表位标记。
IF 3.8 3区 生物学
BMB Reports Pub Date : 2024-01-01
Cheljong Hong, Jun Hee Han, Gue-Ho Hwang, Sangsu Bae, Pil Joon Seo
{"title":"Genome-wide in-locus epitope tagging of Arabidopsis proteins using prime editors.","authors":"Cheljong Hong, Jun Hee Han, Gue-Ho Hwang, Sangsu Bae, Pil Joon Seo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prime editors (PEs), which are CRISPR-Cas9 nickase (H840A)-reverse transcriptase fusion proteins programmed with prime editing guide RNAs (pegRNAs), can not only edit bases but also install transversions, insertions, or deletions without both donor DNA and double-strand breaks at the target DNA. As the demand for in-locus tagging is increasing, to reflect gene expression dynamics influenced by endogenous genomic contexts, we demonstrated that PEs can be used to introduce the hemagglutinin (HA) epitope tag to a target gene locus, enabling molecular and biochemical studies using in-locus tagged plants. To promote genome-wide in-locus tagging, we also implemented a publicly available database that designs pegRNAs for in-locus tagging of all the Arabidopsis genes. [BMB Reports 2024; 57(1): 66-70].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"66-70"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Harnessing CRISPR-Cas adaptation for RNA recording and beyond. 利用 CRISPR-Cas 适应性进行 RNA 记录及其他。
IF 3.8 3区 生物学
BMB Reports Pub Date : 2024-01-01
Gyeong-Seok Oh, Seongjin An, Sungchul Kim
{"title":"Harnessing CRISPR-Cas adaptation for RNA recording and beyond.","authors":"Gyeong-Seok Oh, Seongjin An, Sungchul Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prokaryotes encode clustered regularly interspaced short palindromic repeat (CRISPR) arrays and CRISPR-associated (Cas) genes as an adaptive immune machinery. CRISPR-Cas systems effectively protect hosts from the invasion of foreign enemies, such as bacteriophages and plasmids. During a process called 'adaptation', non-self-nucleic acid fragments are acquired as spacers between repeats in the host CRISPR array, to establish immunological memory. The highly conserved Cas1-Cas2 complexes function as molecular recorders to integrate spacers in a time course manner, which can subsequently be expressed as crRNAs complexed with Cas effector proteins for the RNAguided interference pathways. In some of the RNA-targeting type III systems, Cas1 proteins are fused with reverse transcriptase (RT), indicating that RT-Cas1-Cas2 complexes can acquire RNA transcripts for spacer acquisition. In this review, we summarize current studies that focus on the molecular structure and function of the RT-fused Cas1-Cas2 integrase, and its potential applications as a directional RNA-recording tool in cells. Furthermore, we highlight outstanding questions for RT-Cas1-Cas2 studies and future directions for RNA-recording CRISPR technologies. [BMB Reports 2024; 57(1): 40-49].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"40-49"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Applications of CRISPR technologies to the development of gene and cell therapy. 将 CRISPR 技术应用于基因和细胞疗法的开发。
IF 3.8 3区 生物学
BMB Reports Pub Date : 2024-01-01
Chul-Sung Park, Omer Habib, Younsu Lee, Junho K Hur
{"title":"Applications of CRISPR technologies to the development of gene and cell therapy.","authors":"Chul-Sung Park, Omer Habib, Younsu Lee, Junho K Hur","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Advancements in gene and cell therapy have resulted in novel therapeutics for diseases previously considered incurable or challenging to treat. Among the various contributing technologies, genome editing stands out as one of the most crucial for the progress in gene and cell therapy. The discovery of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and the subsequent evolution of genetic engineering technology have markedly expanded the field of target-specific gene editing. Originally studied in the immune systems of bacteria and archaea, the CRISPR system has demonstrated wide applicability to effective genome editing of various biological systems including human cells. The development of CRISPR-based base editing has enabled directional cytosine-tothymine and adenine-to-guanine substitutions of select DNA bases at the target locus. Subsequent advances in prime editing further elevated the flexibility of the edit multiple consecutive bases to desired sequences. The recent CRISPR technologies also have been actively utilized for the development of in vivo and ex vivo gene and cell therapies. We anticipate that the medical applications of CRISPR will rapidly progress to provide unprecedented possibilities to develop novel therapeutics towards various diseases. [BMB Reports 2024; 57(1): 2-11].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"2-11"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interplay between epigenome and 3D chromatin structure. 表观基因组与三维染色质结构之间的相互作用
IF 3.8 3区 生物学
BMB Reports Pub Date : 2023-12-05 DOI: 10.5483/bmbrep.2023-0197
Minhee Park, Man-Hyuk Han, Dariya Issagulova
{"title":"Interplay between epigenome and 3D chromatin structure.","authors":"Minhee Park, Man-Hyuk Han, Dariya Issagulova","doi":"10.5483/bmbrep.2023-0197","DOIUrl":"https://doi.org/10.5483/bmbrep.2023-0197","url":null,"abstract":"Epigenetic mechanisms, primarily mediated through histone and DNA modifications, play a pivotal role in orchestrating the functional identity of a cell and its response to environmental cues. Similarly, the spatial arrangement of chromatin within the three-dimensional (3D) nucleus has been recognized as a significant factor influencing genomic function. Investigating the relationship between epigenetic regulation and 3D chromatin structure has revealed correlation and causality between these processes, from the global alignment of average chromatin structure with chromatin marks to the nuanced correlations at smaller scales. This review aims to dissect the biological significance and the interplay between the epigenome and 3D chromatin structure, while also exploring the underlying molecular mechanisms. By synthesizing insights from both experimental and modeling perspectives, we seek to provide a comprehensive understanding of cellular functions.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":"125 46","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138599087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of cellular prion protein in immune system. 细胞朊病毒蛋白在免疫系统中的作用。
IF 3.8 3区 生物学
BMB Reports Pub Date : 2023-12-01
Seunghwa Cha, Mi-Yeon Kim
{"title":"The role of cellular prion protein in immune system.","authors":"Seunghwa Cha, Mi-Yeon Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Numerous studies have investigated the cellular prion protein (PrP<sup>C</sup>) since its discovery. These investigations have explained that its structure is predominantly composed of alpha helices and short beta sheet segments, and when its abnormal scrapie isoform (PrP<sup>Sc</sup>) is infected, PrP<sup>Sc</sup> transforms the PrP<sup>C</sup>, leading to prion diseases, including Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in cattle. Given its ubiquitous distribution across a variety of cellular types, the PrP<sup>C</sup> manifests a diverse range of biological functions, including cell-cell adhesion, neuroprotection, signalings, and oxidative stress response. PrP<sup>C</sup> is also expressed in immune tissues, and its functions in these tissues include the activation of immune cells and the formation of secondary lymphoid tissues, such as the spleen and lymph nodes. Moreover, high expression of PrP<sup>C</sup> in immune cells plays a crucial role in the pathogenesis of prion diseases. In addition, it affects inflammation and the development and progression of cancer via various mechanisms. In this review, we discuss the studies on the role of PrP<sup>C</sup> from various immunological perspectives. [BMB Reports 2023; 56(12): 645-650].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"645-650"},"PeriodicalIF":3.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Distinct sets of lysosomal genes define synucleinopathy and tauopathy. 溶酶体基因的不同集合定义了突触核蛋白病和tau病。
IF 3.8 3区 生物学
BMB Reports Pub Date : 2023-12-01
Kyu Won Oh, Dong-Kyu Kim, Ao-Lin Hsu, Seung-Jae Lee
{"title":"Distinct sets of lysosomal genes define synucleinopathy and tauopathy.","authors":"Kyu Won Oh, Dong-Kyu Kim, Ao-Lin Hsu, Seung-Jae Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Neurodegenerative diseases are characterized by distinct protein aggregates, such as those of α-synuclein and tau. Lysosomal defect is a key contributor to the accumulation and propagation of aberrant protein aggregates in these diseases. The discoveries of common proteinopathies in multiple forms of lysosomal storage diseases (LSDs) and the identification of some LSD genes as susceptible genes for those proteinopathies suggest causative links between LSDs and the proteinopathies. The present study hypothesized that defects in lysosomal genes will differentially affect the propagation of α-synuclein and tau proteins, thereby determining the progression of a specific proteinopathy. We established an imaging-based high-contents screening (HCS) system in Caenorhabditis elegans (C. elegans) model, by which the propagation of α-synuclein or tau is measured by fluorescence intensity. Using this system, we performed RNA interference (RNAi) screening to induce a wide range of lysosomal malfunction through knock down of 79 LSD genes, and to obtain the candidate genes with significant change in protein propagation. While some LSD genes commonly affected both α-synuclein and tau propagation, our study identified the distinct sets of LSD genes that differentially regulate the propagation of either α-synuclein or tau. The specificity and efficacy of these LSD genes were retained in the disease-related phenotypes, such as pharyngeal pumping behavior and life span. This study suggests that distinct lysosomal genes differentially regulate the propagation of α-synuclein and tau, and offer a steppingstone to understanding disease specificity. [BMB Reports 2023; 56(12): 657-662].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"657-662"},"PeriodicalIF":3.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SARS-CoV-2 infection induces expression and secretion of lipocalin-2 and regulates iron in a human lung cancer xenograft model. 在人肺癌癌症异种移植物模型中,SARS-CoV-2感染诱导硫运载蛋白-2的表达和分泌并调节铁。
IF 3.8 3区 生物学
BMB Reports Pub Date : 2023-12-01
Sangkyu Park, Dongbum Kim, Jinsoo Kim, Hyung-Joo Kwon, Younghee Lee
{"title":"SARS-CoV-2 infection induces expression and secretion of lipocalin-2 and regulates iron in a human lung cancer xenograft model.","authors":"Sangkyu Park, Dongbum Kim, Jinsoo Kim, Hyung-Joo Kwon, Younghee Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to various clinical symptoms including anemia. Lipocalin-2 has various biological functions, including defense against bacterial infections through iron sequestration, and it serves as a biomarker for kidney injury. In a human protein array, we observed increased lipocalin-2 expression due to parental SARS-CoV-2 infection in the Calu-3 human lung cancer cell line. The secretion of lipocalin-2 was also elevated in response to parental SARS-CoV-2 infection, and the SARS-CoV-2 Alpha, Beta, and Delta variants similarly induced this phenomenon. In a Calu-3 implanted mouse xenograft model, parental SARSCoV- 2 and Delta variant induced lipocalin-2 expression and secretion. Additionally, the iron concentration increased in the Calu-3 tumor tissues and decreased in the serum due to infection. In conclusion, SARS-CoV-2 infection induces the production and secretion of lipocalin-2, potentially resulting in a decrease in iron concentration in serum. Because the concentration of iron ions in the blood is associated with anemia, this phenomenon could contribute to developing anemia in COVID-19 patients. [BMB Reports 2023; 56(12): 669-674].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"669-674"},"PeriodicalIF":3.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nonsense-mediated mRNA decay, a simplified view of a complex mechanism. 有义介导的 mRNA 衰变,复杂机制的简化视角。
IF 3.8 3区 生物学
BMB Reports Pub Date : 2023-12-01
Julie Carrard, Fabrice Lejeune
{"title":"Nonsense-mediated mRNA decay, a simplified view of a complex mechanism.","authors":"Julie Carrard, Fabrice Lejeune","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Nonsense-mediated mRNA decay (NMD) is both a quality control mechanism and a gene regulation pathway. It has been studied for more than 30 years, with an accumulation of many mechanistic details that have often led to debate and hence to different models of NMD activation, particularly in higher eukaryotes. Two models seem to be opposed, since the first requires intervention of the exon junction complex (EJC) to recruit NMD factors downstream of the premature termination codon (PTC), whereas the second involves an EJC-independent mechanism in which NMD factors concentrate in the 3'UTR to initiate NMD in the presence of a PTC. In this review we describe both models, giving recent molecular details and providing experimental arguments supporting one or the other model. In the end it is certainly possible to imagine that these two mechanisms co-exist, rather than viewing them as mutually exclusive. [BMB Reports 2023; 56(12): 625-632].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"625-632"},"PeriodicalIF":3.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interplay between epigenome and 3D chromatin structure. 表观基因组与三维染色质结构之间的相互作用
IF 2.9 3区 生物学
BMB Reports Pub Date : 2023-12-01
Man-Hyuk Han, Dariya Issagulova, Minhee Park
{"title":"Interplay between epigenome and 3D chromatin structure.","authors":"Man-Hyuk Han, Dariya Issagulova, Minhee Park","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Epigenetic mechanisms, primarily mediated through histone and DNA modifications, play a pivotal role in orchestrating the functional identity of a cell and its response to environmental cues. Similarly, the spatial arrangement of chromatin within the threedimensional (3D) nucleus has been recognized as a significant factor influencing genomic function. Investigating the relationship between epigenetic regulation and 3D chromatin structure has revealed correlation and causality between these processes, from the global alignment of average chromatin structure with chromatin marks to the nuanced correlations at smaller scales. This review aims to dissect the biological significance and the interplay between the epigenome and 3D chromatin structure, while also exploring the underlying molecular mechanisms. By synthesizing insights from both experimental and modeling perspectives, we seek to provide a comprehensive understanding of cellular functions. [BMB Reports 2023; 56(12): 633-644].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"633-644"},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fatty acid oxidation regulates cellular senescence by modulating the autophagy-SIRT1 axis. 脂肪酸氧化通过调节自噬-SIRT1轴调节细胞衰老
IF 3.8 3区 生物学
BMB Reports Pub Date : 2023-12-01
Seungyeon Yang, Subin Moon, Soojung Claire Hur, Seung Min Jeong
{"title":"Fatty acid oxidation regulates cellular senescence by modulating the autophagy-SIRT1 axis.","authors":"Seungyeon Yang, Subin Moon, Soojung Claire Hur, Seung Min Jeong","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Senescence, a cellular process through which damaged or dysfunctional cells suppress the cell cycle, contributes to aging or age-related functional decline. Cell metabolism has been closely correlated with aging processes, and it has been widely recognized that metabolic changes underlie the cellular alterations that occur with aging. Here, we report that fatty acid oxidation (FAO) serves as a critical regulator of cellular senescence and uncover the underlying mechanism by which FAO inhibition induces senescence. Pharmacological or genetic ablation of FAO results in a p53-dependent induction of cellular senescence in human fibroblasts, whereas enhancing FAO suppresses replicative senescence. We found that FAO inhibition promotes cellular senescence through acetyl-CoA, independent of energy depletion. Mechanistically, increased formation of autophagosomes following FAO inhibition leads to a reduction in SIRT1 protein levels, thereby contributing to senescence induction. Finally, we found that inhibition of autophagy or enforced expression of SIRT1 can rescue the induction of senescence as a result of FAO inhibition. Collectively, our study reveals a distinctive role for the FAO-autophagy-SIRT1 axis in the regulation of cellular senescence. [BMB Reports 2023; 56(12): 651-656].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"651-656"},"PeriodicalIF":3.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10172834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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