Sun-young Park , Dongyoon Shin , Young So Yoon , Sujin Park , Seung-Soon Im , Yeongshin Kim , Young-Soo Kim , CheolSoo Choi , Man-Wook Hur
{"title":"TAT38 and TAT38 mimics potently inhibit adipogenesis by repressing C/EBPα, PPARγ, Pi-PPARγ, and SREBP1 expression","authors":"Sun-young Park , Dongyoon Shin , Young So Yoon , Sujin Park , Seung-Soon Im , Yeongshin Kim , Young-Soo Kim , CheolSoo Choi , Man-Wook Hur","doi":"10.1016/j.bbagrm.2024.195030","DOIUrl":"10.1016/j.bbagrm.2024.195030","url":null,"abstract":"<div><p>Antiretroviral therapy-naive people living with HIV possess less fat than people without HIV. Previously, we found that HIV-1 transactivator of transcription (TAT) decreases fat in <em>ob/ob</em> mice. The TAT38 (a.a. 20–57) is important in the inhibition of adipogenesis and contains three functional domains: Cys-ZF domain (a.a. 20–35 TACTNCYCAKCCFQVC), core-domain (a.a. 36–46, FITKALGISYG), and protein transduction domain (PTD)(a.a. 47–57, RAKRRQRRR). Interestingly, the TAT38 region interacts with the Cyclin T1 of the P-TEFb complex, of which expression increases during adipogenesis. The X-ray crystallographic structure of the complex showed that the Cys-ZF and the core domain bind to the Cyclin T1 via hydrophobic interactions. To prepare TAT38 mimics with structural and functional similarities to TAT38, we replaced the core domain with a hydrophobic aliphatic amino acid (from carbon numbers 5 to 8). The TAT38 mimics with 6-hexanoic amino acid (TAT38 Ahx (C6)) and 7-heptanoic amino acid (TAT38 Ahp (C7)) inhibited adipogenesis of 3T3-L1 potently, reduced cellular triglyceride content, and decreased body weight of diet-induced obese (DIO) mice by 10.4–11 % in two weeks. The TAT38 and the TAT38 mimics potently repressed the adipogenic transcription factors genes, C/EBPα, PPARγ, and SREBP1. Also, they inhibit the phosphorylation of PPARγ. The TAT peptides may be promising candidates for development into a drug against obesity or diabetes.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195030"},"PeriodicalIF":4.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140760884","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}
Yuzhu Wang , Meng Chen , Haoyu Ma , Zhongliang Zhu , Jie Gao , Shanhui Liao , Jiahai Zhang , Xiaoming Tu
{"title":"Structural basis of the interaction between TFIIS and Leo1 from Arabidopsis thaliana","authors":"Yuzhu Wang , Meng Chen , Haoyu Ma , Zhongliang Zhu , Jie Gao , Shanhui Liao , Jiahai Zhang , Xiaoming Tu","doi":"10.1016/j.bbagrm.2024.195027","DOIUrl":"https://doi.org/10.1016/j.bbagrm.2024.195027","url":null,"abstract":"","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195027"},"PeriodicalIF":4.7,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825535","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}
{"title":"The nucleolus: Coordinating stress response and genomic stability","authors":"Katiuska González-Arzola","doi":"10.1016/j.bbagrm.2024.195029","DOIUrl":"https://doi.org/10.1016/j.bbagrm.2024.195029","url":null,"abstract":"<div><p>The perception that the nucleoli are merely the organelles where ribosome biogenesis occurs is challenged. Only around 30 % of nucleolar proteins are solely involved in producing ribosomes. Instead, the nucleolus plays a critical role in controlling protein trafficking during stress and, according to its dynamic nature, undergoes continuous protein exchange with nucleoplasm under various cellular stressors. Hence, the concept of nucleolar stress has evolved as cellular insults that disrupt the structure and function of the nucleolus. Considering the emerging role of this organelle in DNA repair and the fact that rDNAs are the most fragile genomic loci, therapies targeting the nucleoli are increasingly being developed. Besides, drugs that target ribosome synthesis and induce nucleolar stress can be used in cancer therapy. In contrast, agents that regulate nucleolar activity may be a potential treatment for neurodegeneration caused by abnormal protein accumulation in the nucleolus. Here, I explore the roles of nucleoli beyond their ribosomal functions, highlighting the factors triggering nucleolar stress and their impact on genomic stability.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195029"},"PeriodicalIF":4.7,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650468","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}
{"title":"The role of nucleotide opening dynamics in facilitated target search by DNA-repair proteins","authors":"Sujeet Kumar Mishra , Sangeeta , Dieter W. Heermann , Arnab Bhattacherjee","doi":"10.1016/j.bbagrm.2024.195026","DOIUrl":"https://doi.org/10.1016/j.bbagrm.2024.195026","url":null,"abstract":"<div><p>Preserving the genomic integrity stands a fundamental necessity, primarily achieved by the DNA repair proteins through their continuous patrolling on the DNA in search of lesions. However, comprehending how even a single base-pair lesion can be swiftly and specifically recognized amidst millions of base-pair sites remains a formidable challenge. In this study, we employ extensive molecular dynamics simulations using an appropriately tuned model of both protein and DNA to probe the underlying molecular principles. Our findings reveal that the dynamics of a non-canonical base generate an entropic signal that guides the one-dimensional search of a repair protein, thereby facilitating the recognition of the lesion site. The width of the funnel perfectly aligns with the one-dimensional diffusion length of DNA-binding proteins. The generic mechanism provides a physical basis for rapid recognition and specificity of DNA damage sensing and recognition.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195026"},"PeriodicalIF":4.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140631667","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}
{"title":"The essential link: How STAT3 connects tumor metabolism to immunity","authors":"Shu Zhong, Jingjing Tong","doi":"10.1016/j.bbagrm.2024.195028","DOIUrl":"https://doi.org/10.1016/j.bbagrm.2024.195028","url":null,"abstract":"<div><p>Immunotherapy is a promising and long-lasting tumor treatment method, but it is challenged by the complex metabolism of tumors. To optimize immunotherapy, it is essential to further investigate the key proteins that regulate tumor metabolism and immune response. STAT3 plays a crucial role in regulating tumor dynamic metabolism and affecting immune cell function by responding to various cytokines and growth factors, which can be used as a potential target for immunotherapy. This review focuses on the crosstalk between STAT3 and tumor metabolism (including glucose, lipid, and amino acid metabolism) and its impact on the differentiation and function of immune cells such as T cells, tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs), and reveals potential treatment strategies.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195028"},"PeriodicalIF":4.7,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140620880","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}
{"title":"Illuminating ligand-induced dynamics in nuclear receptors through MD simulations","authors":"Tracy Yu , Nishanti Sudhakar , C. Denise Okafor","doi":"10.1016/j.bbagrm.2024.195025","DOIUrl":"https://doi.org/10.1016/j.bbagrm.2024.195025","url":null,"abstract":"<div><p>Nuclear receptors (NRs) regulate gene expression in critical physiological processes, with their functionality finely tuned by ligand-induced conformational changes. While NRs may sometimes undergo significant conformational motions in response to ligand-binding, these effects are more commonly subtle and challenging to study by traditional structural or biophysical methods. Molecular dynamics (MD) simulations are a powerful tool to bridge the gap between static protein-ligand structures and dynamical changes that govern NR function. Here, we summarize a handful of recent studies that apply MD simulations to study NRs. We present diverse methodologies for analyzing simulation data with a detailed examination of the information each method can yield. By delving into the strengths, limitations and unique contributions of these tools, this review provides guidance for extracting meaningful data from MD simulations to advance the goal of understanding the intricate mechanisms by which ligands orchestrate a range of functional outcomes in NRs.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195025"},"PeriodicalIF":4.7,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S187493992400021X/pdfft?md5=7d5eb13de1394345e0d37b70621dfa76&pid=1-s2.0-S187493992400021X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140607084","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}
{"title":"Global control of RNA polymerase II","authors":"Alexander Gillis, Scott Berry","doi":"10.1016/j.bbagrm.2024.195024","DOIUrl":"10.1016/j.bbagrm.2024.195024","url":null,"abstract":"<div><p>RNA polymerase II (Pol II) is the multi-protein complex responsible for transcribing all protein-coding messenger RNA (mRNA). Most research on gene regulation is focused on the mechanisms controlling <em>which genes</em> are transcribed <em>when</em>, or on the mechanics of transcription. How global Pol II activity is determined receives comparatively less attention. Here, we follow the life of a Pol II molecule from ‘assembly of the complex’ to nuclear import, enzymatic activity, and degradation. We focus on how Pol II spends its time in the nucleus, and on the two-way relationship between Pol II abundance and activity in the context of homeostasis and global transcriptional changes.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195024"},"PeriodicalIF":4.7,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874939924000208/pdfft?md5=66407b36023b5a96807e0166eddceb5e&pid=1-s2.0-S1874939924000208-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327338","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}
{"title":"Transcriptional landscape of long non-coding RNAs (lncRNAs) and its implication in viral diseases","authors":"Ankita Rai, Tannu Bhagchandani, Ravi Tandon","doi":"10.1016/j.bbagrm.2024.195023","DOIUrl":"10.1016/j.bbagrm.2024.195023","url":null,"abstract":"<div><p>Long non-coding RNAs (lncRNAs) are RNA transcripts of size >200 bp that do not translate into proteins. Emerging data revealed that viral infection results in systemic changes in the host at transcriptional level. These include alterations in the lncRNA expression levels and triggering of antiviral immune response involving several effector molecules and diverse signalling pathways. Thus, lncRNAs have emerged as an essential mediatory element at distinct phases of the virus infection cycle. The complete eradication of the viral disease requires more precise and novel approach, thus manipulation of the lncRNAs could be one of them. This review shed light upon the existing knowledge of lncRNAs wherein the implication of differentially expressed lncRNAs in blood-borne, air-borne, and vector-borne viral diseases and its promising therapeutic applications under clinical settings has been discussed. It further enhances our understanding of the complex interplay at host-pathogen interface with respect to lncRNA expression and function.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195023"},"PeriodicalIF":4.7,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186392","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}
Priyanka Yadav, Raja Tamilselvan, Harita Mani, Kusum Kumari Singh
{"title":"MicroRNA-mediated regulation of nonsense-mediated mRNA decay factors: Insights into microRNA prediction tools and profiling techniques","authors":"Priyanka Yadav, Raja Tamilselvan, Harita Mani, Kusum Kumari Singh","doi":"10.1016/j.bbagrm.2024.195022","DOIUrl":"10.1016/j.bbagrm.2024.195022","url":null,"abstract":"<div><p>Nonsense-mediated mRNA decay (NMD) stands out as a prominent RNA surveillance mechanism within eukaryotes, meticulously overseeing both RNA abundance and integrity by eliminating aberrant transcripts. These defective transcripts are discerned through the concerted efforts of translating ribosomes, eukaryotic release factors (eRFs), and trans-acting NMD factors, with Up-Frameshift 3 (UPF3) serving as a noteworthy component. Remarkably, in humans, UPF3 exists in two paralogous forms, UPF3A (UPF3) and UPF3B (UPF3X). Beyond its role in quality control, UPF3 wields significant influence over critical cellular processes, including neural development, synaptic plasticity, and axon guidance. However, the precise regulatory mechanisms governing UPF3 remain elusive.</p><p>MicroRNAs (miRNAs) emerge as pivotal post-transcriptional gene regulators, exerting substantial impact on diverse pathological and physiological pathways. This comprehensive review encapsulates our current understanding of the intricate regulatory nexus between NMD and miRNAs, with particular emphasis on the essential role played by UPF3B in neurodevelopment. Additionally, we bring out the significance of the 3’-untranslated region (3’-UTR) as the molecular bridge connecting NMD and miRNA-mediated gene regulation. Furthermore, we provide an in-depth exploration of diverse computational tools tailored for the prediction of potential miRNA targets. To complement these computational approaches, we delineate experimental techniques designed to validate predicted miRNA-mRNA interactions, empowering readers with the knowledge necessary to select the most appropriate methodology for their specific research objectives.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195022"},"PeriodicalIF":4.7,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029634","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}
{"title":"Histone H3K4ac, as a marker of active transcription start sites and enhancers, plays roles in histone eviction and RNA transcription","authors":"Jin Kang , Yujin Kang , AeRi Kim","doi":"10.1016/j.bbagrm.2024.195021","DOIUrl":"10.1016/j.bbagrm.2024.195021","url":null,"abstract":"<div><p>The lysine 4 of histone H3 (H3K4) can be methylated or acetylated into four states: H3K4me1, H3K4me2, H3K4me3, or H3K4ac. Unlike H3K4 methylation, the genome-wide distribution and functional roles of H3K4ac remain unclear. To understand the relationship of acetylation with methylation at H3K4 and to explore the roles of H3K4ac in the context of chromatin, we analyzed H3K4ac across the human genome and compared it with H3K4 methylation in K562 cells. H3K4ac was positively correlated with H3K4me1/2/3 in reciprocal analysis. A decrease in H3K4ac through the mutation of the histone acetyltransferase p300 reduced H3K4me1 and H3K4me3 at the H3K4ac peaks. H3K4ac was also impaired by H3K4me depletion in the histone methyltransferase MLL3/4-mutated cells. H3K4ac peaks were enriched at enhancers in addition to the transcription start sites (TSSs) of genes. H3K4ac of TSSs and enhancers was positively correlated with mRNA and eRNA transcription. A decrease in H3K4ac reduced H3K4me3 and H3K4me1 in TSSs and enhancers, respectively, and inhibited the eviction of histone H3 from them. The mRNA transcription of highly transcribed genes was affected by the reduced H3K4ac. Interestingly, H3K4ac played a redundant role with regard to H3K27ac in eRNA transcription. These results indicate that H3K4ac serves as a marker of both active TSSs and enhancers and plays a role in histone eviction and RNA transcription by leading to H3K4me1/3.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195021"},"PeriodicalIF":4.7,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991980","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}