EMBO Reports最新文献_第3页

Humour uncovers the wide landscape of life : From laughter to freedom. 幽默揭示了生活的广阔前景：从欢笑到自由。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-03 DOI: 10.1038/s44319-025-00494-6

Vladimir Leksa

引用次数: 0

DPP8/9 processing of human AK2 unmasks an IAP binding motif. DPP8/9处理人类AK2揭示了IAP结合基序。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-01 Epub Date: 2025-05-01 DOI: 10.1038/s44319-025-00455-z

Kim J Lapacz, Konstantin Weiss, Franziska Mueller, Yuxing Xue, Simon Poepsel, Matthias Weith, Tanja Bange, Jan Riemer

{"title":"DPP8/9 processing of human AK2 unmasks an IAP binding motif.","authors":"Kim J Lapacz, Konstantin Weiss, Franziska Mueller, Yuxing Xue, Simon Poepsel, Matthias Weith, Tanja Bange, Jan Riemer","doi":"10.1038/s44319-025-00455-z","DOIUrl":"10.1038/s44319-025-00455-z","url":null,"abstract":"Adenylate kinase 2 (AK2) is localized in the intermembrane space of mitochondria, where it ensures efficient adenine nucleotide exchange between cytosol and mitochondria. For mitochondrial import, AK2 relies on the MIA40 disulphide relay system. Its cytosolic stability is subject to regulation through N-terminal processing by the dipeptidyl peptidases DPP8 and DPP9, which sensitize AK2 for proteasomal degradation. Here, we find that cytosolic AK2 degradation is mediated by Inhibitors of Apoptosis (IAPs), a class of E3 ligases that interacts with target proteins by binding to IAP-binding motifs (IBM). We have identified an IBM at the very end of AK2's novel N-terminus, which becomes exposed due to processing by DPP8/9. N-terminal acetylation mediated by the N-acetyltransferase NatA prevents this AK2-IAP interaction, therefore stabilizing AK2 in the cytosol. Performing a genome-wide in silico screen, we could identify 129 potential substrates in which an IBM becomes potentially unmasked by DPP8/9 processing. For one of these potential substrates, EIF2A, we demonstrate its targeting to IAPs after IBM exposure by DPP8/9 indicating that DPP8/9-mediated unmasking of IBMs is a general phenomenon.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2819-2835"},"PeriodicalIF":6.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Controlled anarchy. 无政府状态控制。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-01 Epub Date: 2025-05-13 DOI: 10.1038/s44319-025-00468-8

Fiona M Watt

引用次数: 0

A transcription factor module mediating C₂ photosynthesis in the Brassicaceae. 一个介导十字花科植物C2光合作用的转录因子模块。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-01 Epub Date: 2025-05-01 DOI: 10.1038/s44319-025-00461-1

Patrick J Dickinson, Sebastian Triesch, Urte Schlüter, Andreas P M Weber, Julian M Hibberd

{"title":"A transcription factor module mediating C2 photosynthesis in the Brassicaceae.","authors":"Patrick J Dickinson, Sebastian Triesch, Urte Schlüter, Andreas P M Weber, Julian M Hibberd","doi":"10.1038/s44319-025-00461-1","DOIUrl":"10.1038/s44319-025-00461-1","url":null,"abstract":"C4 photosynthesis has arisen from the ancestral C3 state in over sixty lineages of angiosperms. It is widely accepted that an early step in C4 evolution is associated with the appearance of so-called C2 photosynthesis caused by loss of glycine decarboxylase activity from mesophyll cells followed by activation in the bundle sheath. Although changes in cis to a distal enhancer upstream of the P-subunit of GLYCINE DECARBOXYLASE (GLDP) from C2 Moricandia enable loss of expression from mesophyll cells, the mechanism then allowing GLDP expression in the bundle sheath is not known. Here we identify a MYC-MYB transcription factor module previously associated with the control of glucosinolate biosynthesis as the basis of this foundational event in the evolution of C2 photosynthesis. Specifically, we find that in the C3 state this MYC-MYB module already patterns GLDP expression to bundle sheath cells. As a consequence, when GLDP expression is lost from the mesophyll, the MYC-MYB dependent expression in the bundle sheath is revealed. Evolution of C2 photosynthesis is thus associated with a MYC-MYB based transcriptional network already present in the C3 state. This work identifies a molecular genetic mechanism underlying the bundle sheath accumulation of glycine decarboxylase required for C2 photosynthesis and thus a fundamental step in the evolution of C4 photosynthesis.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3024-3031"},"PeriodicalIF":6.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Transcriptomic changes including p53 dysregulation prime DNMT3A mutant cells for transformation. 转录组学改变，包括p53失调，导致DNMT3A突变细胞转化。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-01 Epub Date: 2025-04-30 DOI: 10.1038/s44319-025-00450-4

Erin M Lawrence, Amali Cooray, Andrew J Kueh, Martin Pal, Lin Tai, Alexandra L Garnham, Connie S N Li-Wai-Suen, Hannah Vanyai, Quentin Gouil, James Lancaster, Sylvie Callegari, Lauren Whelan, Elizabeth Lieschke, Annabella Thomas, Andreas Strasser, Yang Liao, Wei Shi, Andrew H Wei, Marco J Herold

{"title":"Transcriptomic changes including p53 dysregulation prime DNMT3A mutant cells for transformation.","authors":"Erin M Lawrence, Amali Cooray, Andrew J Kueh, Martin Pal, Lin Tai, Alexandra L Garnham, Connie S N Li-Wai-Suen, Hannah Vanyai, Quentin Gouil, James Lancaster, Sylvie Callegari, Lauren Whelan, Elizabeth Lieschke, Annabella Thomas, Andreas Strasser, Yang Liao, Wei Shi, Andrew H Wei, Marco J Herold","doi":"10.1038/s44319-025-00450-4","DOIUrl":"10.1038/s44319-025-00450-4","url":null,"abstract":"DNMT3A mutations are prevalent in haematologic malignancies. In our mouse model the murine homologue (R878H) of the human 'hotspot' R882H mutation is introduced into the mouse Dnmt3a locus. This results in globally reduced DNA methylation in all tissues. Mice with heterozygous R878H DNMT3A mutations develop γ-radiation induced thymic lymphoma more rapidly than control mice, suggesting a vulnerability to stress stimuli in Dnmt3aR878H/+ cells. In competitive transplantations, Dnmt3aR878H/+ Lin-Sca-1+Kit+ (LSK) haematopoietic stem/progenitor cells (HSPCs) have a competitive advantage over WT HSPCs, indicating a self-renewal phenotype at the expense of differentiation. RNA sequencing of Dnmt3aR878H/+ LSKs exposed to low dose γ-radiation shows downregulation of the p53 pathway compared to γ-irradiated WT LSKs. Accordingly, reduced PUMA expression is observed by flow cytometry in the bone marrow of γ-irradiated Dnmt3aR878H/+ mice due to impaired p53 signalling. These findings provide new insights into how DNMT3A mutations cause subtle changes in the transcriptome of LSK cells which contribute to their increased self-renewal and propensity for malignant transformation.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2855-2882"},"PeriodicalIF":6.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Articulating the need to minimize moral incursions in research : The least infringement condition. 阐明研究中道德侵害最小化的必要性：最小侵害条件。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-01 Epub Date: 2025-05-27 DOI: 10.1038/s44319-025-00490-w

Jeremy Sugarman

引用次数: 0

Disrupted glucocorticoid receptor cell signalling causes a ciliogenesis defect in the fetal mouse renal tubule. 糖皮质激素受体细胞信号传导中断导致胎鼠肾小管纤毛发生缺陷。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-01 Epub Date: 2025-04-17 DOI: 10.1038/s44319-025-00454-0

Kelly L Short, Jianshen Lao, Rachel Lam, Julie L M Moreau, Judy Ng, Mehran Piran, Alexander N Combes, Denny L Cottle, Timothy J Cole

{"title":"Disrupted glucocorticoid receptor cell signalling causes a ciliogenesis defect in the fetal mouse renal tubule.","authors":"Kelly L Short, Jianshen Lao, Rachel Lam, Julie L M Moreau, Judy Ng, Mehran Piran, Alexander N Combes, Denny L Cottle, Timothy J Cole","doi":"10.1038/s44319-025-00454-0","DOIUrl":"10.1038/s44319-025-00454-0","url":null,"abstract":"Primary cilia are cell signalling and environment sensing organelles and have important roles during embryogenesis and homeostasis. We demonstrate glucocorticoid signalling is essential for normal cilia formation in mouse and human renal tubules. RNA sequencing of E18.5 kidneys from glucocorticoid receptor (GR) null mice identified significant reductions in key ciliogenesis-related genes including Ccp110, Cep97, Cep290 and Kif3a. Confocal microscopy reveals abnormal, stunted cilia on proximal tubules, podocytes, and collecting duct cells in mice with global or conditional deletion of GR. In contrast, activation of GR signalling with dexamethasone in human kidney organoids or mouse IMCD3 cells increases cilia length, an effect blocked by the GR antagonist RU486. Analysis of GR-null kidney extracts demonstrates reduced levels of pERK and SUFU identifying potential cell pathway crosstalk with GR signalling that coordinately regulate ciliogenesis in the renal tubule. Finally, dexamethasone reduces Aurora kinase A levels, a factor driving cilia disassembly and implicated in the pathogenesis of polycystic kidney disease.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2883-2909"},"PeriodicalIF":6.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

RNase H1 and Sen1 ensure that transient TERRA R-loops promote the repair of short telomeres. RNase H1和Sen1确保瞬时TERRA r -环促进短端粒的修复。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-01 Epub Date: 2025-05-22 DOI: 10.1038/s44319-025-00469-7

Fabio Bento, Matteo Longaretti, Vanessa Borges Pires, Arianna Lockhart, Brian Luke

{"title":"RNase H1 and Sen1 ensure that transient TERRA R-loops promote the repair of short telomeres.","authors":"Fabio Bento, Matteo Longaretti, Vanessa Borges Pires, Arianna Lockhart, Brian Luke","doi":"10.1038/s44319-025-00469-7","DOIUrl":"10.1038/s44319-025-00469-7","url":null,"abstract":"Telomere repeat-containing RNA (TERRA) is transcribed at telomeres and forms RNA-DNA hybrids. In budding yeast, the presence of RNA-DNA hybrids at short telomeres promotes homology-directed repair (HDR) and prevents accelerated replicative senescence. RNA-DNA hybrids at telomeres have also been demonstrated to prevent 5'end resection, an essential step for HDR. In accordance, we now demonstrate that, not only the presence, but also the removal, of RNA-DNA hybrids drives HDR at shortened telomeres during replicative senescence. Although RNase H2 is absent from short telomeres, it is quickly compensated for by the recruitment of RNase H1 and Sen1. The recruitment of RNase H1 is essential to allow for the loading of Rad51, consistent with the notion that RNA-DNA hybrids prevent Exo1-mediated end resection. In the absence of RNase H1 or Sen1 function, yeast cultures prematurely enter replicative senescence in the absence of telomerase. Furthermore, the delayed senescence phenotype observed when RNase H2 is deleted, depends on the presence of RNase H1 and Sen1. This study demonstrates the importance of transient RNA-DNA hybrids at short telomeres to regulate senescence.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3032-3044"},"PeriodicalIF":6.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Ganglioside GT1b prevents selective spinal synapse removal following peripheral nerve injury. 神经节苷脂GT1b防止周围神经损伤后选择性脊髓突触移除。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-01 Epub Date: 2025-04-30 DOI: 10.1038/s44319-025-00452-2

Jaesung Lee, Kyungchul Noh, Subeen Lee, Kwang Hwan Kim, Seohyun Chung, Hyoungsub Lim, Minkyu Hwang, Joon-Hyuk Lee, Won-Suk Chung, Sunghoe Chang, Sung Joong Lee

{"title":"Ganglioside GT1b prevents selective spinal synapse removal following peripheral nerve injury.","authors":"Jaesung Lee, Kyungchul Noh, Subeen Lee, Kwang Hwan Kim, Seohyun Chung, Hyoungsub Lim, Minkyu Hwang, Joon-Hyuk Lee, Won-Suk Chung, Sunghoe Chang, Sung Joong Lee","doi":"10.1038/s44319-025-00452-2","DOIUrl":"10.1038/s44319-025-00452-2","url":null,"abstract":"After peripheral nerve injury, the structure of the spinal cord is actively regulated by glial cells, contributing to the chronicity of neuropathic pain. However, the mechanism by which peripheral nerve injury leads to synaptic imbalance remains elusive. Here, we use a pH-reporter system and find that nerve injury triggers a reorganization of excitatory synapses that is influenced by the accumulation of the ganglioside GT1b at afferent terminals. GT1b acts as a protective signal against nerve injury-induced spinal synapse elimination. Inhibition of GT1b-synthesis increases glial phagocytosis of excitatory pre-synapses and reduces excitatory synapses post-injury. In vitro analyses reveal a positive correlation between GT1b accumulation and the frequency of pre-synaptic calcium activity, with GT1b-mediated suppression of glial phagocytosis occurring through SYK dephosphorylation. Our study highlights GT1b's pivotal role in preventing synapse elimination after nerve injury and offers new insight into the molecular underpinning of activity-dependent synaptic stability and glial phagocytosis.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2994-3023"},"PeriodicalIF":6.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

An integrated anatomical, functional and evolutionary view of the Drosophila olfactory system. 果蝇嗅觉系统的综合解剖、功能和进化观点。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-01 Epub Date: 2025-05-19 DOI: 10.1038/s44319-025-00476-8

Richard Benton, Jérôme Mermet, Andre Jang, Keita Endo, Steeve Cruchet, Karen Menuz

{"title":"An integrated anatomical, functional and evolutionary view of the Drosophila olfactory system.","authors":"Richard Benton, Jérôme Mermet, Andre Jang, Keita Endo, Steeve Cruchet, Karen Menuz","doi":"10.1038/s44319-025-00476-8","DOIUrl":"10.1038/s44319-025-00476-8","url":null,"abstract":"The Drosophila melanogaster olfactory system is one of the most intensively studied parts of the nervous system in any animal. Composed of ~50 independent olfactory neuron classes, with several associated hygrosensory and thermosensory pathways, it has been subject to diverse types of experimental analyses. However, synthesizing the available information is limited by the incomplete data and inconsistent nomenclature found in the literature. In this work, we first \"complete\" the peripheral sensory map through the identification of a previously uncharacterized antennal sensory neuron population expressing Or46aB, and the definition of an exceptional \"hybrid\" olfactory neuron class comprising functional Or and Ir receptors. Second, we survey developmental, anatomical, connectomic, functional, and evolutionary studies to generate an integrated dataset and associated visualizations of these sensory neuron pathways, creating an unprecedented resource. Third, we illustrate the utility of the dataset to reveal relationships between different organizational properties of this sensory system, and the new questions these stimulate. Such examples emphasize the power of this resource to promote further understanding of the construction, function, and evolution of these neural circuits.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3204-3225"},"PeriodicalIF":6.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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