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Nuclear RNA: a transcription-dependent regulator of chromatin structure. 核糖核酸：依赖转录的染色质结构调节器。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20230787
Jon Stocks, Nick Gilbert
{"title":"Nuclear RNA: a transcription-dependent regulator of chromatin structure.","authors":"Jon Stocks, Nick Gilbert","doi":"10.1042/BST20230787","DOIUrl":"10.1042/BST20230787","url":null,"abstract":"<p><p>Although the majority of RNAs are retained in the nucleus, their significance is often overlooked. However, it is now becoming clear that nuclear RNA forms a dynamic structure through interacting with various proteins that can influence the three-dimensional structure of chromatin. We review the emerging evidence for a nuclear RNA mesh or gel, highlighting the interplay between DNA, RNA and RNA-binding proteins (RBPs), and assessing the critical role of protein and RNA in governing chromatin architecture. We also discuss a proposed role for the formation and regulation of the nuclear gel in transcriptional control. We suggest that it may concentrate the transcriptional machinery either by direct binding or inducing RBPs to form microphase condensates, nanometre sized membraneless structures with distinct properties to the surrounding medium and an enrichment of particular macromolecules.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1605-1615"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854621","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
Non-Mendelian transmission of X chromosomes: mechanisms and impact on sex ratios and population dynamics in different breeding systems. X 染色体的非孟德尔传播：机制及其对不同育种系统中性别比例和种群动态的影响。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20231411
Sally Adams, Andre Pires-daSilva
{"title":"Non-Mendelian transmission of X chromosomes: mechanisms and impact on sex ratios and population dynamics in different breeding systems.","authors":"Sally Adams, Andre Pires-daSilva","doi":"10.1042/BST20231411","DOIUrl":"10.1042/BST20231411","url":null,"abstract":"<p><p>The non-Mendelian transmission of sex chromosomes during gametogenesis carries significant implications, influencing sex ratios and shaping evolutionary dynamics. Here we focus on known mechanisms that drive non-Mendelian inheritance of X chromosomes during spermatogenesis and their impact on population dynamics in species with different breeding systems. In Drosophila and mice, X-linked drivers targeting Y-bearing sperm for elimination or limiting their fitness, tend to confer unfavourable effects, prompting the evolution of suppressors to mitigate their impact. This leads to a complex ongoing evolutionary arms race to maintain an equal balance of males and females. However, in certain insects and nematodes with XX/X0 sex determination, the preferential production of X-bearing sperm through atypical meiosis yields wild-type populations with highly skewed sex ratios, suggesting non-Mendelian transmission of the X may offer selective advantages in these species. Indeed, models suggest X-meiotic drivers could bolster population size and persistence under certain conditions, challenging the conventional view of their detrimental effects. Furthering our understanding of the diverse mechanisms and evolutionary consequences of non-Mendelian transmission of X chromosomes will provide insights into genetic inheritance, sex determination, and population dynamics, with implications for fundamental research and practical applications.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1777-1784"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987355","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
Plant supercomplex I + III2 structure and function: implications for the growing field. 植物超级复合体 I + III2 的结构和功能：对不断发展的领域的影响。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20230947
Maria Maldonado
{"title":"Plant supercomplex I + III2 structure and function: implications for the growing field.","authors":"Maria Maldonado","doi":"10.1042/BST20230947","DOIUrl":"10.1042/BST20230947","url":null,"abstract":"<p><p>Mitochondrial respiration is major source of chemical energy for all free-living eukaryotes. Nevertheless, the mechanisms of the respiratory complexes and supercomplexes remain poorly understood. Here, I review recent structural and functional investigations of plant supercomplex I + III2 from Arabidopsis thaliana and Vigna radiata. I discuss commonalities, open questions and implications for complex I, complex III2 and supercomplexes in plants and non-plants. Studies across further clades will enhance our understanding of respiration and the potential universal mechanisms of its complexes and supercomplexes.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1647-1659"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035122","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
Early heart development: examining the dynamics of function-form emergence. 早期心脏发育：研究功能形式出现的动态过程。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20230546
Noémie Combémorel, Natasha Cavell, Richard C V Tyser
{"title":"Early heart development: examining the dynamics of function-form emergence.","authors":"Noémie Combémorel, Natasha Cavell, Richard C V Tyser","doi":"10.1042/BST20230546","DOIUrl":"10.1042/BST20230546","url":null,"abstract":"<p><p>During early embryonic development, the heart undergoes a remarkable and complex transformation, acquiring its iconic four-chamber structure whilst concomitantly contracting to maintain its essential function. The emergence of cardiac form and function involves intricate interplays between molecular, cellular, and biomechanical events, unfolding with precision in both space and time. The dynamic morphological remodelling of the developing heart renders it particularly vulnerable to congenital defects, with heart malformations being the most common type of congenital birth defect (∼35% of all congenital birth defects). This mini-review aims to give an overview of the morphogenetic processes which govern early heart formation as well as the dynamics and mechanisms of early cardiac function. Moreover, we aim to highlight some of the interplay between these two processes and discuss how recent findings and emerging techniques/models offer promising avenues for future exploration. In summary, the developing heart is an exciting model to gain fundamental insight into the dynamic relationship between form and function, which will augment our understanding of cardiac congenital defects and provide a blueprint for potential therapeutic strategies to treat disease.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1579-1589"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557909","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
Progress in multifactorial single-cell chromatin profiling methods. 多因素单细胞染色质谱分析方法的进展。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20231471
Tim Stuart
{"title":"Progress in multifactorial single-cell chromatin profiling methods.","authors":"Tim Stuart","doi":"10.1042/BST20231471","DOIUrl":"10.1042/BST20231471","url":null,"abstract":"<p><p>Chromatin states play a key role in shaping overall cellular states and fates. Building a complete picture of the functional state of chromatin in cells requires the co-detection of several distinct biochemical aspects. These span DNA methylation, chromatin accessibility, chromosomal conformation, histone posttranslational modifications, and more. While this certainly presents a challenging task, over the past few years many new and creative methods have been developed that now enable co-assay of these different aspects of chromatin at single cell resolution. This field is entering an exciting phase, where a confluence of technological improvements, decreased sequencing costs, and computational innovation are presenting new opportunities to dissect the diversity of chromatin states present in tissues, and how these states may influence gene regulation. In this review, I discuss the spectrum of current experimental approaches for multifactorial chromatin profiling, highlight some of the experimental and analytical challenges, as well as some areas for further innovation.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1827-1839"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632554","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
Understanding P-Rex regulation: structural breakthroughs and emerging perspectives. 了解 P-Rex 调节：结构性突破和新观点。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20231546
Gareth D Jones, Andrew M Ellisdon
{"title":"Understanding P-Rex regulation: structural breakthroughs and emerging perspectives.","authors":"Gareth D Jones, Andrew M Ellisdon","doi":"10.1042/BST20231546","DOIUrl":"10.1042/BST20231546","url":null,"abstract":"<p><p>Rho GTPases are a family of highly conserved G proteins that regulate numerous cellular processes, including cytoskeleton organisation, migration, and proliferation. The 20 canonical Rho GTPases are regulated by ∼85 guanine nucleotide exchange factors (GEFs), with the largest family being the 71 Diffuse B-cell Lymphoma (Dbl) GEFs. Dbl GEFs promote GTPase activity through the highly conserved Dbl homology domain. The specificity of GEF activity, and consequently GTPase activity, lies in the regulation and structures of the GEFs themselves. Dbl GEFs contain various accessory domains that regulate GEF activity by controlling subcellular localisation, protein interactions, and often autoinhibition. This review focuses on the two phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3)-dependent Rac exchangers (P-Rex), particularly the structural basis of P-Rex1 autoinhibition and synergistic activation. First, we discuss structures that highlight the conservation of P-Rex catalytic and phosphoinositide binding activities. We then explore recent breakthroughs in uncovering the structural basis for P-Rex1 autoinhibition and detail the proposed minimal two-step model of how PI(3,4,5)P3 and Gβγ synergistically activate P-Rex1 at the membrane. Additionally, we discuss the further layers of P-Rex regulation provided by phosphorylation and P-Rex2-PTEN coinhibitory complex formation, although these mechanisms remain incompletely understood. Finally, we leverage the available data to infer how cancer-associated mutations in P-Rex2 destabilise autoinhibition and evade PTEN coinhibitory complex formation, leading to increased P-Rex2 GEF activity and driving cancer progression and metastasis.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1849-1860"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632555","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
Enzymes of sphingolipid metabolism as transducers of metabolic inputs. 鞘脂代谢酶是新陈代谢输入的转换器。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20231442
Fabiola N Velazquez, Chiara Luberto, Daniel Canals, Yusuf A Hannun
{"title":"Enzymes of sphingolipid metabolism as transducers of metabolic inputs.","authors":"Fabiola N Velazquez, Chiara Luberto, Daniel Canals, Yusuf A Hannun","doi":"10.1042/BST20231442","DOIUrl":"10.1042/BST20231442","url":null,"abstract":"<p><p>Sphingolipids (SLs) constitute a discrete subdomain of metabolism, and they display both structural and signaling functions. Accumulating evidence also points to intimate connections between intermediary metabolism and SL metabolism. Given that many SLs exhibit bioactive properties (i.e. transduce signals), these raise the possibility that an important function of SLs is to relay information on metabolic changes into specific cell responses. This could occur at various levels. Some metabolites are incorporated into SLs, whereas others may initiate regulatory or signaling events that, in turn, modulate SL metabolism. In this review, we elaborate on the former as it represents a poorly appreciated aspect of SL metabolism, and we develop the hypothesis that the SL network is highly sensitive to several specific metabolic changes, focusing on amino acids (serine and alanine), various fatty acids, choline (and ethanolamine), and glucose.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1795-1808"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888412","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
Computational design of de novo bioenergetic membrane proteins. 全新生物能膜蛋白的计算设计。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20231347
Benjamin J Hardy, Paul Curnow
{"title":"Computational design of de novo bioenergetic membrane proteins.","authors":"Benjamin J Hardy, Paul Curnow","doi":"10.1042/BST20231347","DOIUrl":"10.1042/BST20231347","url":null,"abstract":"<p><p>The major energy-producing reactions of biochemistry occur at biological membranes. Computational protein design now provides the opportunity to elucidate the underlying principles of these processes and to construct bioenergetic pathways on our own terms. Here, we review recent achievements in this endeavour of 'synthetic bioenergetics', with a particular focus on new enabling tools that facilitate the computational design of biocompatible de novo integral membrane proteins. We use recent examples to showcase some of the key computational approaches in current use and highlight that the overall philosophy of 'surface-swapping' - the replacement of solvent-facing residues with amino acids bearing lipid-soluble hydrophobic sidechains - is a promising avenue in membrane protein design. We conclude by highlighting outstanding design challenges and the emerging role of AI in sequence design and structure ideation.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1737-1745"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490673","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
Transcriptional bursting: from fundamentals to novel insights. 转录突变：从基本原理到新见解。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20231286
Daniel Hebenstreit, Pradip Karmakar
{"title":"Transcriptional bursting: from fundamentals to novel insights.","authors":"Daniel Hebenstreit, Pradip Karmakar","doi":"10.1042/BST20231286","DOIUrl":"10.1042/BST20231286","url":null,"abstract":"<p><p>Transcription occurs as irregular bursts in a very wide range of systems, including numerous different species and many genes within these. In this review, we examine the underlying theories, discuss how these relate to experimental measurements, and explore some of the discrepancies that have emerged among various studies. Finally, we consider more recent works that integrate novel concepts, such as the involvement of biomolecular condensates in enhancer-promoter interactions and their effects on the dynamics of transcriptional bursting.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1695-1702"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905791","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
Mechanisms of lysosomal tubulation and sorting driven by LRRK2. LRRK2 驱动溶酶体管化和分选的机制。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20240087
Luis Bonet-Ponce, Jillian H Kluss, Mark R Cookson
{"title":"Mechanisms of lysosomal tubulation and sorting driven by LRRK2.","authors":"Luis Bonet-Ponce, Jillian H Kluss, Mark R Cookson","doi":"10.1042/BST20240087","DOIUrl":"10.1042/BST20240087","url":null,"abstract":"<p><p>Lysosomes are dynamic cellular structures that adaptively remodel their membrane in response to stimuli, including membrane damage. Lysosomal dysfunction plays a central role in the pathobiology of Parkinson's disease (PD). Gain-of-function mutations in Leucine-rich repeat kinase 2 (LRRK2) cause familial PD and genetic variations in its locus increase the risk of developing the sporadic form of the disease. We previously uncovered a process we term LYTL (LYsosomal Tubulation/sorting driven by LRRK2), wherein membrane-damaged lysosomes generate tubules sorted into mobile vesicles. Subsequently, these vesicles interact with healthy lysosomes. LYTL is orchestrated by LRRK2 kinase activity, via the recruitment and phosphorylation of a subset of RAB GTPases. Here, we summarize the current understanding of LYTL and its regulation, as well as the unknown aspects of this process.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1909-1919"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854620","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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