The EMBO Journal最新文献_第8页

When sperm age, their RNA code hits a cliff. 当精子老化时，它们的RNA编码就会跌落悬崖。

The EMBO Journal Pub Date : 2026-03-17 DOI: 10.1038/s44318-026-00743-x

Noriko Osumi

引用次数: 0

Dual ubiquitin signalling by SLOMO controls AUX1 activity and turnover during root gravitropism. SLOMO双泛素信号控制根系向倾斜过程中AUX1的活性和转换。

The EMBO Journal Pub Date : 2026-03-17 DOI: 10.1038/s44318-026-00746-8

Lixia Pan,Shanshuo Zhu,Shao-Li Yang,Nathan Mellor,Francesca R Iacobini,Tingyu Zhu,Pia Neyt,Brigitte van de Cotte,Michaël Vandorpe,Ranjan Swarup,Daniël Van Damme,Markus M Geisler,Kris Gevaert,Leah R Band,Ive De Smet

{"title":"Dual ubiquitin signalling by SLOMO controls AUX1 activity and turnover during root gravitropism.","authors":"Lixia Pan,Shanshuo Zhu,Shao-Li Yang,Nathan Mellor,Francesca R Iacobini,Tingyu Zhu,Pia Neyt,Brigitte van de Cotte,Michaël Vandorpe,Ranjan Swarup,Daniël Van Damme,Markus M Geisler,Kris Gevaert,Leah R Band,Ive De Smet","doi":"10.1038/s44318-026-00746-8","DOIUrl":"https://doi.org/10.1038/s44318-026-00746-8","url":null,"abstract":"Gravity-directed growth ensures that shoots and roots grow upwards and downwards, respectively. To achieve this, the organ's angle with respect to gravity drives the asymmetric redistribution of the plant hormone auxin and consequently differential elongation, thus creating a curvature of the organ. In addition to efflux transporters, the auxin influx transporter AUXIN RESISTANT 1 (AUX1) is essential for auxin redistribution during root gravitropism. Here, we show that the F-box protein SLOMO regulates AUX1 via two distinct mechanisms. First, SLOMO promotes proteolytic degradation of AUX1, possibly in an indirect manner. Second, SLOMO controls the ubiquitination of K261, K264, and K266, thus potentially affecting AUX1 auxin transport properties that are regulated by these residues. This reveals a dual mode of SLOMO-mediated regulation of AUX1, including a novel, non-proteolytic role for SLOMO-mediated ubiquitination in addition to SLOMO-mediated degradation of AUX1.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A functional overlap between actively transcribed genes and chromatin insulator elements. 活跃转录基因和染色质绝缘子元件之间的功能重叠。

The EMBO Journal Pub Date : 2026-03-16 DOI: 10.1038/s44318-026-00730-2

Lucy J Cornell,Caroline L Harrold,Susannah Holliman,Felice Tsang,Matthew E Gosden,Lars L P Hanssen,Rosa Stolper,Damien J Downes,Daniel Biggs,Chris Preece,Samy Alghadban,Jacqueline A Sharpe,Benjamin Davies,Jacqueline A Sloane-Stanley,Jim R Hughes,Douglas R Higgs,Mira T Kassouf

{"title":"A functional overlap between actively transcribed genes and chromatin insulator elements.","authors":"Lucy J Cornell,Caroline L Harrold,Susannah Holliman,Felice Tsang,Matthew E Gosden,Lars L P Hanssen,Rosa Stolper,Damien J Downes,Daniel Biggs,Chris Preece,Samy Alghadban,Jacqueline A Sharpe,Benjamin Davies,Jacqueline A Sloane-Stanley,Jim R Hughes,Douglas R Higgs,Mira T Kassouf","doi":"10.1038/s44318-026-00730-2","DOIUrl":"https://doi.org/10.1038/s44318-026-00730-2","url":null,"abstract":"The mammalian genome is organised into large topologically associating domains (TADs) and smaller sub-TADs or enhancer-promoter loops, which may contribute to the regulation of gene expression. These dynamic structures arise, at least partly, via cohesin-mediated loop extrusion delimited by insulator elements. By studying the structure and function of the alpha-globin locus during erythroid differentiation, we have previously shown that the juxtaposition of the enhancers and promoters during this process partly depends on cohesin-mediated loop extrusion, which appears to be delimited by 12 largely convergently orientated CTCF boundary elements. To define the downstream boundary of the sub-TAD, we removed four CTCF sites in informative combinations. This showed that rather than CTCF insulators, it is the transcriptionally active alpha-globin gene that defines the downstream boundary of the sub-TAD. Further, insertion of actively transcribed fragments of the α-globin gene between the enhancers and native genes leads to a reduction in native α-globin expression and accumulation of cohesin at the insertion site. This highlights an overlap in the functional role of the fundamental elements of the genome.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"94 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147464987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

When RNA goes off script: ensuring transcript fidelity in transgene expression. 当RNA偏离脚本：确保转基因表达中的转录保真度。

The EMBO Journal Pub Date : 2026-03-16 DOI: 10.1038/s44318-026-00733-z

Rachel Anderson,Christalyn Ausler,Ankur Jain

引用次数: 0

Graded versus ON/OFF control in quantitative gene expression and epigenetic memory. 定量基因表达和表观遗传记忆的分级与ON/OFF控制。

The EMBO Journal Pub Date : 2026-03-16 DOI: 10.1038/s44318-026-00750-y

Caroline Dean,Martin Howard

引用次数: 0

Feeder-free yet still naïve: improved method for capturing human pluripotent stem cells. 无饲料，但仍然naïve：改进的方法捕获人类多能干细胞。

The EMBO Journal Pub Date : 2026-03-12 DOI: 10.1038/s44318-026-00713-3

Masaki Yagi,Konrad Hochedlinger

引用次数: 0

ZAP targets aberrant mRNA transcripts encoding proteins with defective signal peptides for degradation. ZAP针对编码有缺陷的信号肽的蛋白质的异常mRNA转录物进行降解。

The EMBO Journal Pub Date : 2026-03-12 DOI: 10.1038/s44318-026-00720-4

Akruti Shah,Aaztli R Coria,Britnie Santiago Membréno,Emilien Orgebin,Jennifer T Miller,Wilfried Guiblet,Colin Chih-Chien Wu

{"title":"ZAP targets aberrant mRNA transcripts encoding proteins with defective signal peptides for degradation.","authors":"Akruti Shah,Aaztli R Coria,Britnie Santiago Membréno,Emilien Orgebin,Jennifer T Miller,Wilfried Guiblet,Colin Chih-Chien Wu","doi":"10.1038/s44318-026-00720-4","DOIUrl":"https://doi.org/10.1038/s44318-026-00720-4","url":null,"abstract":"The endoplasmic reticulum (ER) is an important site for accurate folding and processing of secretory and membrane proteins. Signal peptides within such proteins are recognized by the signal recognition particle (SRP), which guides them to the ER. When this process is impaired, cells rely on quality control mechanisms to prevent the accumulation of misfolded or mislocalized proteins. One of these mechanisms, known as regulation of aberrant protein production (RAPP), detects nascent proteins with aberrant signal peptides and degrades their mRNA templates. Using functional genetic screens, we identify the zinc finger antiviral protein (ZAP) as a key component of the RAPP pathway. Proteomics and enhanced UV-crosslinking and immunoprecipitation (eCLIP) experiments reveal that the short isoform ZAP-S associates with SRP components and facilitates degradation of aberrant mRNAs. ZAP-S recognizes faulty proteins early in their biogenesis and targets their corresponding mRNAs for degradation. Loss of ZAP activates the unfolded protein response and the downstream integrated stress response, highlighting its central role in safeguarding protein targeting and maintaining cellular homeostasis.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Serum coating enables feeder-free culture of naive human pluripotent stem cells preserving developmental potential. 血清包衣使原始人类多能干细胞保持发育潜力的无饲料培养成为可能。

The EMBO Journal Pub Date : 2026-03-12 DOI: 10.1038/s44318-026-00714-2

Giada Rossignoli,Michael Oberhuemer,Ida Sophie Brun,Irene Zorzan,Anna Osnato,Anne Wenzel,Emiel van Genderen,Andrea Drusin,Giorgia Panebianco,Nicolò Magri,Moritz Becker,Mairim Alexandra Solis,Chiara Colantuono,Sam Samuël Franciscus Allegonda van Knippenberg,Thi Xuan Ai Pham,Sherif Khodeer,Paolo Grumati,Davide Cacchiarelli,Paolo Martini,Nicolas Rivron,Vincent Pasque,Jan Jakub Żylicz,Martin Leeb,Graziano Martello

{"title":"Serum coating enables feeder-free culture of naive human pluripotent stem cells preserving developmental potential.","authors":"Giada Rossignoli,Michael Oberhuemer,Ida Sophie Brun,Irene Zorzan,Anna Osnato,Anne Wenzel,Emiel van Genderen,Andrea Drusin,Giorgia Panebianco,Nicolò Magri,Moritz Becker,Mairim Alexandra Solis,Chiara Colantuono,Sam Samuël Franciscus Allegonda van Knippenberg,Thi Xuan Ai Pham,Sherif Khodeer,Paolo Grumati,Davide Cacchiarelli,Paolo Martini,Nicolas Rivron,Vincent Pasque,Jan Jakub Żylicz,Martin Leeb,Graziano Martello","doi":"10.1038/s44318-026-00714-2","DOIUrl":"https://doi.org/10.1038/s44318-026-00714-2","url":null,"abstract":"Naive human pluripotent stem cells (hPSCs) represent a pre-implantation epiblast state able to efficiently differentiate into embryonic and extraembryonic pre-implantation lineages and to self-organise in vitro into blastocyst-like structures called blastoids. Naive hPSC maintenance routinely relies on co-culture with mouse embryonic fibroblast (MEFs) as feeder cells, a method prone to variability and analytical confounders. Here, we describe a feeder-free culture system based on serum coating that supports long-term maintenance of naive hPSCs. Across five laboratories, 30 serum batches were evaluated for the expansion of eight naive hPSCs lines for up to 25 passages. Mass spectrometry analysis identified fibronectin and collagens as extracellular matrix proteins consistently present in serum coating. Cells cultured on serum coating displayed growth kinetics, clonogenic capacity, mutation rates, and global gene expression profiles comparable to MEF-based cultures. Importantly, serum-cultured naive hPSCs efficiently underwent germ layer specification, retained trophectoderm competence, and generated blastoids with efficiency similar to MEF-based cultures. Collectively, serum coating provides a scalable, cost-effective, and robust alternative to feeder-based systems, preserving genomic stability and developmental potential while eliminating MEF-associated disadvantages and variability. This platform facilitates large-scale applications of naive hPSCs and enables more reproducible mechanistic studies.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protease-mediated PRC1 dissociation promotes H2AK119ub remodeling during stress responses. 蛋白酶介导的PRC1解离促进应激反应中的H2AK119ub重塑。

The EMBO Journal Pub Date : 2026-03-11 DOI: 10.1038/s44318-026-00729-9

Wei Cui,Qingyang Li,Jinsong Wei,Ting Zhou,Haozhe Zhu,Delai Huang,Shuai Wang,Jianan Gao,Ru Zhou,Zeyu Sun,Hua Ruan,Li Jan Lo,Ting Tao,Jun Chen,Jinrong Peng,Hui Shi

引用次数: 0

The importance of regulated resource reallocation during dynamic environmental shifts in yeast. 酵母在动态环境变化中调节资源再分配的重要性。

The EMBO Journal Pub Date : 2026-03-11 DOI: 10.1038/s44318-026-00727-x

Rachel A Kocik,Eli G Cytrynbaum,Jamie M Ahrens,Megan N McClean,Audrey P Gasch

{"title":"The importance of regulated resource reallocation during dynamic environmental shifts in yeast.","authors":"Rachel A Kocik,Eli G Cytrynbaum,Jamie M Ahrens,Megan N McClean,Audrey P Gasch","doi":"10.1038/s44318-026-00727-x","DOIUrl":"https://doi.org/10.1038/s44318-026-00727-x","url":null,"abstract":"Many organisms maintain generalized stress responses activated by adverse conditions. A common theme is the induction of stress-defense proteins with reduced production of growth-promoting proteins, including ribosomes. Yet the precise roles of these coupled programs are difficult to dissect. Here, we investigated Saccharomyces cerevisiae responding to salt as a model stressor. We used molecular, genomic, and single-cell microfluidic methods to examine the interplay between transient induction of stress-defense genes and coordinated repression of growth-promoting genes in the yeast environmental stress response (ESR). Loss of transcriptional inducers Msn2/4 accelerates growth during multiple mild stress doses, at the expense of acquired tolerance to subsequent severe stresses. In contrast, loss of Dot6/Tod6 repressors of growth-promoting genes delays stress acclimation, showing that gene repression accommodates the cost of the Msn2/4 response. Msn2/4 bind the DOT6 promoter, influence Dot6 abundance and activation dynamics, and are required for full repression of Dot6 targets and other growth-promoting genes. Thus, Msn2/4 participate in regulating resource reallocation needed to induce their transcripts, underscoring a common theme in stress responses utilized in other organisms.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0