Journal of Molecular Biology最新文献_第9页

High-resolution Sequencing Reveals that the Paf1 Complex May be a Conserved Transcription Elongation Factor for Eukaryotic RNA Polymerase I 高分辨率测序显示，Paf1复合体可能是真核RNA聚合酶I的保守转录延伸因子。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-05-19 DOI: 10.1016/j.jmb.2025.169220

Abigail K. Huffines, Naiheng J. Yang, David A. Schneider

{"title":"High-resolution Sequencing Reveals that the Paf1 Complex May be a Conserved Transcription Elongation Factor for Eukaryotic RNA Polymerase I","authors":"Abigail K. Huffines, Naiheng J. Yang, David A. Schneider","doi":"10.1016/j.jmb.2025.169220","DOIUrl":"10.1016/j.jmb.2025.169220","url":null,"abstract":"<div><div>In eukaryotes, at least three Pols (I, II, and III) are responsible for synthesizing unique RNA products. Many <em>trans</em>-acting factors affect the efficiency of transcription by the three Pols. Some of these factors influence more than one of the nuclear Pols. One such factor is polymerase-associated factor 1 complex (Paf1C). Paf1C, composed of five subunits in <em>Saccharomyces cerevisiae</em> (yeast), has been shown to promote transcription by Pols I and II and is conserved across eukaryotes. Although several studies have demonstrated that Paf1C associates with Pol I machinery, its roles in ribosomal RNA synthesis are not well-defined. In this study, we used native elongating transcript sequencing (NET-seq), to investigate the effect of the loss of two of the five Paf1C subunits (Paf1 and Cdc73) on Pol I occupancy at single-nucleotide resolution in yeast. We found that in both <em>paf</em>1Δ and <em>cdc</em>73Δ mutants, there was a significant reduction in Pol I occupancy at the 5′ end of the DNA template as compared to WT yeast, accompanied by other occupancy pattern changes throughout the gene. To complement these results, we also analyzed a PRO-seq dataset that was generated with DLD1 mammalian cells. Interestingly, we found that when Paf1C was knocked-down, there was also a reduction in the occupancy of Pol I at the 5′ end of the gene, consistent with our NET-seq analysis. Overall, our results support the conclusion that Paf1C is an important transcription elongation factor for Pol I and may play a conserved role across species.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 17","pages":"Article 169220"},"PeriodicalIF":4.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Evolution and Implications of the Inosine tRNA Modification 肌苷tRNA修饰的进化及其意义。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-05-17 DOI: 10.1016/j.jmb.2025.169187

Peter T.S. van der Gulik , Wouter D. Hoff

{"title":"The Evolution and Implications of the Inosine tRNA Modification","authors":"Peter T.S. van der Gulik , Wouter D. Hoff","doi":"10.1016/j.jmb.2025.169187","DOIUrl":"10.1016/j.jmb.2025.169187","url":null,"abstract":"<div><div>Ever since the legendary publication by Francis Crick in <em>JMB</em> introducing the wobble hypothesis in 1966, inosine has been a permanent part of molecular biology. This review aims to integrate the rich array of novel insights emerging from subsequent research on the adenine-to-inosine modification of tRNA, with an emphasis on the results obtained during the last 5 years. Both the grand panorama of 4 billion years of evolution of life and the medical implications of defects in inosine modification will be reviewed.</div><div>The most salient insights are that: (1) inosine at position 34 (the first position in the anticodon) is not universally present in the tree of life; (2) in many bacteria just a single homodimeric enzyme (TadA) is responsible for both tRNA inosine modification and mRNA inosine modification; (3) rapid progress is currently being made both in the molecular understanding of the heterodimeric ADAT2/ADAT3 enzyme responsible for inosine modifications in eukaryotes and in experimental capabilities for monitoring both the cytoplasmic tRNA pool and their modifications; (4) for selected tRNAs, inosine modification at position 37 has been demonstrated but this modification remains under-studied; (5) modification of tRNAs known to contain inosine can be incomplete; (6) the GC content of the T-stem is of great importance for wobble behavior, including wobbling behavior of inosine; and (7) the tRNA inosine modification is of direct relevance to human disease.</div><div>In summary, research on inosine continues to yield important novel insights.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 16","pages":"Article 169187"},"PeriodicalIF":4.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Pseudouridine Modifications in Transfer RNA and tRNA Pseudouridine Synthases 转运RNA和tRNA假尿嘧啶合酶中的假尿嘧啶修饰。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-05-16 DOI: 10.1016/j.jmb.2025.169183

Chie Tomikawa

{"title":"Pseudouridine Modifications in Transfer RNA and tRNA Pseudouridine Synthases","authors":"Chie Tomikawa","doi":"10.1016/j.jmb.2025.169183","DOIUrl":"10.1016/j.jmb.2025.169183","url":null,"abstract":"<div><div>Among the various modifications found in transfer RNAs, pseudouridine occurs the most frequently in all organisms and is also found in other RNA species including ribosomal, messenger, small nuclear, small nucleolar, and transfer-messenger RNA. Since the first gene encoding a tRNA pseudouridine synthase (<em>truA</em>) was discovered in 1978, many pseudouridine synthases have been identified, some of which are specific for one site in tRNA, while others act at multiple sites. Furthermore, some enzymes catalyze pseudouridine modification of not only tRNA but also ribosomal RNA and small nuclear RNA or messenger RNA. The functions of pseudouridine in tRNA are diverse, from contributing to the stabilization of tRNA structure to having an essential role in accurate protein synthesis (deficiency induces a frameshift in some cases). Some pseudouridine synthases also function as RNA chaperones. In this review, I summarize the reaction mechanism and functions of pseudouridine synthases with reference to the six pseudouridine synthase families, including similarities and variations in domain structures, motifs, and target uracil bases. I also characterize individual enzymes and highlight recently revealed links between pseudouridine/pseudouridine synthases and viral infections and human diseases.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 16","pages":"Article 169183"},"PeriodicalIF":4.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Autophagy Dysfunction and Neurodegeneration: Where Does It Go Wrong? 自噬功能障碍和神经变性：哪里出了问题？

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-05-16 DOI: 10.1016/j.jmb.2025.169219

Daphne Oettinger , Ai Yamamoto

{"title":"Autophagy Dysfunction and Neurodegeneration: Where Does It Go Wrong?","authors":"Daphne Oettinger , Ai Yamamoto","doi":"10.1016/j.jmb.2025.169219","DOIUrl":"10.1016/j.jmb.2025.169219","url":null,"abstract":"<div><div>An infamous hallmark of neurodegenerative diseases is the accumulation of misfolded or unfolded proteins forming inclusions in the brain. The accumulation of these abnormal structures is a mysterious one, given that cells devote significant resources to integrate complementary pathways to ensure proteome integrity and proper protein folding. Aberrantly folded protein species are rapidly targeted for disposal by the ubiquitin–proteasome system (UPS), and even if this should fail, and the species accumulates, the cell can also rely on the lysosome-mediated degradation pathways of autophagy. Despite the many safeguards in place, failure to maintain protein homeostasis commonly occurs during, or preceding, the onset of disease. Over the last decade and a half, studies suggest that the failure of autophagy may explain the disruption in protein homeostasis observed in disease. In this review, we will examine how the highly complex cells of the brain can become vulnerable to failure of aggregate clearance at specific points during the processive pathway of autophagy, contributing to aggregate accumulation in brains with neurodegenerative disease.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 18","pages":"Article 169219"},"PeriodicalIF":4.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Structure and Mechanism of Aminoacyl-tRNA-Protein L/F- and R-transferases 氨基酰基trna -蛋白L/F-和r -转移酶的结构和机制。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-05-15 DOI: 10.1016/j.jmb.2025.169210

Misti Cartwright , Rajat Kumar Jha , Aaron T. Smith

{"title":"Structure and Mechanism of Aminoacyl-tRNA-Protein L/F- and R-transferases","authors":"Misti Cartwright , Rajat Kumar Jha , Aaron T. Smith","doi":"10.1016/j.jmb.2025.169210","DOIUrl":"10.1016/j.jmb.2025.169210","url":null,"abstract":"<div><div>The aminoacyl-tRNA-protein transferases (also known as aa-transferases) are a class of enzymes that utilize a highly conserved GCN5-related <em>N</em>-acetyltransferase (GNAT) fold to catalyze the post-translational transfer of amino acids from an aminoacylated transfer RNA (tRNA) to an acceptor protein. The two most important subclasses of aa-transferases are the prokaryotic L/F-transferases and the eukaryotic R-transferases (ATE1s). Both subclasses were initially discovered as early as the 1960s, and both share an overlapping function linked to protein degradation: L/F-transferases are known to modify proteins that are ultimately targeted for degradation via the Clp proteolytic pathway, while R-transferases (ATE1s) are known to modify proteins that may be targeted for degradation by the ubiquitin proteasome system (UPS), although many non-degradative fates may also occur. While L/F-transferases have been minimally explored at the cellular level, the R-transferases (ATE1s) have had extensive studies linking them to critical cellular functions. Despite over a half a century passing since their discoveries, X-ray crystallographic and cryo-EM studies have only recently begun to shed light onto the mechanism of these enzymes. This review underscores the functional importance of L/F- and R-transferases (ATE1s) and highlights the recent structural developments in this field with a particular emphasis on the eukaryotic R-transferases (ATE1s). Additionally, this review draws on current structural information to synopsize proposed catalytic and regulatory mechanisms for these enzymes. Finally, this review highlights important structural and mechanistic knowledge gaps in aa-transferase function that should be addressed in order to target these important enzymes for future therapeutic developments.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 17","pages":"Article 169210"},"PeriodicalIF":4.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

PerturbSeq.db: An Integrated Repository for Comprehensive Analysis of Single-cell Perturbation Data db：一个集成的存储库，用于对单细胞扰动数据进行综合分析。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-05-15 DOI: 10.1016/j.jmb.2025.169209

Tongxin He , Xiaoxiao Yang , Yang Tong , Xiaochuan Liu , Yihu Wei , Wenhui Wang , Jiapei Yuan , Yuting Wang , Yang Yang

{"title":"PerturbSeq.db: An Integrated Repository for Comprehensive Analysis of Single-cell Perturbation Data","authors":"Tongxin He , Xiaoxiao Yang , Yang Tong , Xiaochuan Liu , Yihu Wei , Wenhui Wang , Jiapei Yuan , Yuting Wang , Yang Yang","doi":"10.1016/j.jmb.2025.169209","DOIUrl":"10.1016/j.jmb.2025.169209","url":null,"abstract":"<div><div>Single-cell perturbation studies have emerged as a transformative approach in biological research, offering unprecedented insights into cellular responses to genetic and chemical interventions. However, the field faces challenges related to data accessibility and integration. To address this, we present PerturbSeq.db (<span><span>http://bioailab.com/PerturbSeq.db/</span><svg><path></path></svg></span>), a comprehensive database that consolidates and harmonizes single-cell perturbation datasets from a diverse array of sources. PerturbSeq.db comprises 189 datasets from 77 studies, including 165 scRNA-seq and 24 scATAC-seq datasets, spanning approximately 50 distinct cell lines or tissues. To ensure data consistency and comparability, PerturbSeq.db employs a uniform processing pipeline across all datasets. The database is complemented by an interactive, user-friendly interface that facilitates efficient data exploration and analysis, empowering researchers to navigate the complexities of single-cell perturbation data. Overall, PerturbSeq.db serves as a critical resource for the scientific community, providing a comprehensive, well-annotated collection of datasets for analyzing and interpreting the effects of perturbation at the single-cell level.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 17","pages":"Article 169209"},"PeriodicalIF":4.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Structural Insights into Minor and Core Proteins of Bovine Adenovirus 3: Bridging Capsid and Genomic Core 牛腺病毒3次要蛋白和核心蛋白的结构见解：桥接衣壳和基因组核心。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-05-15 DOI: 10.1016/j.jmb.2025.169208

Hao Xiao , Hao Pang , Junquan Zhou , Hao Feng , Jingdong Song , Lingpeng Cheng , Li Wang , Hongrong Liu

引用次数: 0

Computational Resources for Molecular Biology 2025 分子生物学计算资源2025。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-05-15 DOI: 10.1016/j.jmb.2025.169222

David H. Mathews, Rita Casadio, Michael J.E. Sternberg

引用次数: 0

ExoCarta 2024: A Web-based Repository of Small Extracellular Vesicles Cargo ExoCarta 2024：基于网络的小细胞外囊泡货物储存库。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-05-15 DOI: 10.1016/j.jmb.2025.169218

Sriram Gummadi, Sai V. Chitti, Taeyoung Kang, Sanjay Shahi, Suresh Mathivanan, Pamali Fonseka

{"title":"ExoCarta 2024: A Web-based Repository of Small Extracellular Vesicles Cargo","authors":"Sriram Gummadi, Sai V. Chitti, Taeyoung Kang, Sanjay Shahi, Suresh Mathivanan, Pamali Fonseka","doi":"10.1016/j.jmb.2025.169218","DOIUrl":"10.1016/j.jmb.2025.169218","url":null,"abstract":"<div><div>Small extracellular vesicles (sEVs) are small membrane vesicles of endocytic origin secreted into the extracellular environment by all cell types and are known to play a crucial role in intercellular and intracellular communication. These vesicles contain proteins, nucleic acids and lipids and their molecular content reflect the normal and pathophysiological conditions of the host cells. Hence, there is a significant interest in cataloguing the molecular content of sEVs in various conditions as this would aid researchers in understanding the biological roles and altered cellular processes under various diseases and healthy state.</div><div>Here we report ExoCarta (<span><span>https://www.exocarta.org</span><svg><path></path></svg></span>), a freely accessible web-based compendium of studies that encompasses DNA, RNA, proteins, and lipids that are detected in sEVs. ExoCarta catalogues both published and unpublished sEV studies. Current version of ExoCarta contains data from 1249 sEV studies, 119,489 protein entries, 15,868 RNA entries, 3,946 lipid entries and quantitative data for 24,073 entries. QUANT, a quantitative plugin, enables users to compare protein abundance between conditions in a study for gene/protein of interest in real time. ExoCarta provides Gene Ontology (GO) annotations and reactome pathways along with dynamic protein–protein interaction networks, for sEV proteins. A tab delimited file containing the most identified sEV proteins is available for users to download. The integration of sEV DNA studies, QUANT and regularly updated dataset of the ExoCarta database makes it an invaluable resource for small extracellular vesicles researchers across the globe.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 15","pages":"Article 169218"},"PeriodicalIF":4.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Thiamin Pyrophosphate Riboswitch is Affected by Lysine-derived Metabolic Conversion Products in Escherichia coli 硫胺焦磷酸核糖开关受大肠杆菌赖氨酸衍生代谢转化产物的影响。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-05-14 DOI: 10.1016/j.jmb.2025.169207

Shirin Jahangirnejad, Jean-Philippe Côté, Daniel A. Lafontaine

{"title":"The Thiamin Pyrophosphate Riboswitch is Affected by Lysine-derived Metabolic Conversion Products in Escherichia coli","authors":"Shirin Jahangirnejad, Jean-Philippe Côté, Daniel A. Lafontaine","doi":"10.1016/j.jmb.2025.169207","DOIUrl":"10.1016/j.jmb.2025.169207","url":null,"abstract":"<div><div>Riboswitches are 5′ untranslated regulators that control gene expression by specifically monitoring cellular metabolites. Metabolite binding to the riboswitch triggers the genetic regulation at the transcriptional or translational level. Riboswitches typically exhibit high affinities and strong discrimination against non-cognate metabolites, making them well suited to regulate gene expression. Importantly, despite the well characterized cellular processes ensuring metabolic conversion and recycling in bacteria, there is little information about how these processes influence riboswitch regulation mechanisms. Here, we characterize the regulation mechanisms of the lysine-sensing and thiamin pyrophosphate (TPP)-sensing riboswitches in <em>E. coli</em>. In agreement with previous results, our study indicates that the addition of lysine or TPP to the growth medium significantly reduces the expression of the respective riboswitch-regulated mRNAs. Surprisingly, we find that the addition of lysine also leads to a significant decrease in TPP-regulated mRNAs, suggesting that lysine indirectly affects TPP riboswitches. Using mutant strains from the Keio collection, we observe that the effect of lysine on TPP riboswitches is lost when perturbing the lysine degradation process. These data suggest that lysine degradation products may be used to generate TPP through metabolic conversion. In contrast, our results indicate that TPP does not modulate the regulation of the lysine riboswitch, suggesting that TPP does not indirectly affect the lysine riboswitch genetic control. Together, our results indicate that intracellular changes in lysine concentrations can be detected by TPP riboswitches, thus suggesting that riboswitches may be sensitive to cellular stress that are not directly related to their cognate metabolite.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 17","pages":"Article 169207"},"PeriodicalIF":4.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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