EMBO Journal最新文献_第3页

T-cell-derived IFN-γ suppresses T follicular helper cell differentiation and antibody responses. T细胞来源的IFN-γ抑制T滤泡辅助细胞分化和抗体反应。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-01 DOI: 10.1038/s44318-025-00414-3

Eleonora Sala, Maria Nelli, Chiara Laura, Pietro Di Lucia, Cristian Gabriel Beccaria, Elisa B Bono, Marta Mangione, Davide Marotta, Valentina Sperto, Marta Grillo, Leonardo Giustini, Fabio Tosi, Jia Nie, Daehong Kim, Giuliana Furiato, Chiara Malpighi, Eleonora Consolo, Burkhard Becher, Eyal David, Merav Cohen, Amir Giladi, Ido Amit, Remy Bosselut, Luca G Guidotti, Matteo Iannacone, Mirela Kuka

{"title":"T-cell-derived IFN-γ suppresses T follicular helper cell differentiation and antibody responses.","authors":"Eleonora Sala, Maria Nelli, Chiara Laura, Pietro Di Lucia, Cristian Gabriel Beccaria, Elisa B Bono, Marta Mangione, Davide Marotta, Valentina Sperto, Marta Grillo, Leonardo Giustini, Fabio Tosi, Jia Nie, Daehong Kim, Giuliana Furiato, Chiara Malpighi, Eleonora Consolo, Burkhard Becher, Eyal David, Merav Cohen, Amir Giladi, Ido Amit, Remy Bosselut, Luca G Guidotti, Matteo Iannacone, Mirela Kuka","doi":"10.1038/s44318-025-00414-3","DOIUrl":"10.1038/s44318-025-00414-3","url":null,"abstract":"CD4+ T cells play a critical role in antiviral humoral and cellular immune responses. We have previously reported that subcutaneous lymphocytic choriomeningitis virus (s.c. LCMV) infection is characterized by a stark compartmentalization of CD4+ T cells, leading to strong TH1 cell polarization but virtually absent T follicular helper (TFH) cells, key drivers of humoral immunity. Here, we investigate the mechanisms responsible for this impaired TFH differentiation. We show that T-bet+ cells induced by LCMV infection encompass a TH1 cell subset expressing granzyme B (GzmB), and a Tcf-1+ cell subset that retains the potential for TFH differentiation without expressing mature TFH markers. Notably, IFN-γ blockade enables full differentiation of Tcf-1+ cells into TFH cells, formation of germinal centers, and increased antibody production. Suppression of TFH cells by IFN-γ is not directly mediated by CD4+ T cells but rather involves another cell type, likely dendritic cells (DCs). Our study provides novel insights into the mechanisms underlying early CD4+ T-cell polarization and humoral responses to viruses, with the potential to facilitate the development of effective vaccine strategies.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2400-2423"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765681","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

Nanoscale analysis of human G1 and metaphase chromatin in situ. 人G1和中期染色质的纳米级原位分析。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-03-17 DOI: 10.1038/s44318-025-00407-2

Jon Ken Chen, Tingsheng Liu, Shujun Cai, Weimei Ruan, Cai Tong Ng, Jian Shi, Uttam Surana, Lu Gan

{"title":"Nanoscale analysis of human G1 and metaphase chromatin in situ.","authors":"Jon Ken Chen, Tingsheng Liu, Shujun Cai, Weimei Ruan, Cai Tong Ng, Jian Shi, Uttam Surana, Lu Gan","doi":"10.1038/s44318-025-00407-2","DOIUrl":"10.1038/s44318-025-00407-2","url":null,"abstract":"The structure of chromatin at the nucleosome level inside cells is still incompletely understood. Here we present in situ electron cryotomography analyses of chromatin in both G1 and metaphase RPE-1 cells. G1 nucleosomes are concentrated in globular chromatin domains, and metaphase nucleosomes are concentrated in the chromatids. Classification analysis reveals that canonical mononucleosomes, and in some conditions ordered stacked dinucleosomes and mononucleosomes with a disordered gyre-proximal density, are abundant in both cell-cycle states. We do not detect class averages that have more than two stacked nucleosomes or side-by-side dinucleosomes, suggesting that groups of more than two nucleosomes are heterogeneous. Large multi-megadalton structures are abundant in G1 nucleoplasm, but not found in G1 chromatin domains and metaphase chromatin. The macromolecular phenotypes studied here represent a starting point for the comparative analysis of compaction in normal vs. unhealthy human cells, in other cell-cycle states, other organisms, and in vitro chromatin assemblies.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2658-2694"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651782","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

Molecular insights into the effect of 1,6-hexanediol on FUS phase separation. 1,6-己二醇对FUS相分离影响的分子研究。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-25 DOI: 10.1038/s44318-025-00431-2

Tongyin Zheng, Noah Wake, Shuo-Lin Weng, Theodora Myrto Perdikari, Anastasia C Murthy, Jeetain Mittal, Nicolas L Fawzi

{"title":"Molecular insights into the effect of 1,6-hexanediol on FUS phase separation.","authors":"Tongyin Zheng, Noah Wake, Shuo-Lin Weng, Theodora Myrto Perdikari, Anastasia C Murthy, Jeetain Mittal, Nicolas L Fawzi","doi":"10.1038/s44318-025-00431-2","DOIUrl":"10.1038/s44318-025-00431-2","url":null,"abstract":"The alkanediol 1,6-hexanediol has been widely used to dissolve liquid-liquid phase-separated condensates in cells and in vitro, but the details of how it perturbs the molecular interactions underlying liquid-liquid assembly remain unclear. In this study we use a combination of microscopy, nuclear magnetic resonance (NMR) spectroscopy, molecular simulation, and biochemical assays to probe how alkanediols suppress phase separation and why certain isomers are more effective. We show that alkanediols of different lengths and configurations are all capable of disrupting phase separation of the RNA-binding protein Fused in Sarcoma (FUS), although potency varies depending on both geometry and hydrophobicity, which we measure directly. Alkanediols induce a shared pattern of changes to the chemical environment of the protein, to different extents depending on the specific compound. Furthermore, we use lysozyme as a model globular protein to demonstrate that alkanediols decrease the proteins' thermal stability, which is consistent with the view that they disrupt phase separation driven by hydrophobic groups. Conversely, 1,6-hexanediol does not disrupt charge-mediated phase separation, such as FUS RGG-RNA and poly-lysine/poly-aspartic acid condensates. All-atom simulations show that hydroxyl groups in alkanediols mediate interactions with the protein backbone and polar amino acid side chains, while the aliphatic chain allows contact with hydrophobic and aromatic residues, providing a molecular picture of how amphiphilic interactions disrupt FUS phase separation.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2725-2740"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024466","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

The biochemical mechanism of Rho GTPase membrane binding, activation and retention in activity patterning. Rho GTPase膜结合、激活和活性模式保留的生化机制。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-03-31 DOI: 10.1038/s44318-025-00418-z

Michael C Armstrong, Yannic R Weiß, Lila E Hoachlander-Hobby, Ankit A Roy, Ilaria Visco, Alison Moe, Adriana E Golding, Scott D Hansen, William M Bement, Peter Bieling

{"title":"The biochemical mechanism of Rho GTPase membrane binding, activation and retention in activity patterning.","authors":"Michael C Armstrong, Yannic R Weiß, Lila E Hoachlander-Hobby, Ankit A Roy, Ilaria Visco, Alison Moe, Adriana E Golding, Scott D Hansen, William M Bement, Peter Bieling","doi":"10.1038/s44318-025-00418-z","DOIUrl":"10.1038/s44318-025-00418-z","url":null,"abstract":"Rho GTPases form plasma membrane-associated patterns that control the cytoskeleton during cell division, morphogenesis, migration, and wound repair. Their patterning involves transitions between inactive cytosolic and active membrane-bound states, regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and guanine nucleotide dissociation inhibitors (GDIs). However, the relationships between these transitions and role of different regulators remain unclear. We developed a novel reconstitution approach to study Rho GTPase patterning with all major GTPase regulators in a biochemically defined system. We show that Rho GTPase dissociation from RhoGDI is rate-limiting for its membrane association. Rho GTPase activation occurs after membrane insertion, which is unaffected by GEF activity. Once activated, Rho GTPases are retained at the membrane through effector interactions, essential for their enrichment at activation sites. Thus, high cytosolic levels of RhoGDI-bound GTPases ensure a constant supply of inactive GTPases for the membrane, where GEF-mediated activation and effector binding stabilize them. These results delineate the route by which Rho GTPase patterns are established and define stage-dependent roles of its regulators.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2620-2657"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755572","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

Transcriptional landscapes underlying Notch-induced lineage conversion and plasticity of mammary basal cells. notch诱导的乳腺基底细胞谱系转换和可塑性的转录景观。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-04 DOI: 10.1038/s44318-025-00424-1

Candice Merle, Calvin Rodrigues, Atefeh Pourkhalili Langeroudi, Robin Journot, Fabian Rost, Yiteng Dang, Steffen Rulands, Silvia Fre

{"title":"Transcriptional landscapes underlying Notch-induced lineage conversion and plasticity of mammary basal cells.","authors":"Candice Merle, Calvin Rodrigues, Atefeh Pourkhalili Langeroudi, Robin Journot, Fabian Rost, Yiteng Dang, Steffen Rulands, Silvia Fre","doi":"10.1038/s44318-025-00424-1","DOIUrl":"10.1038/s44318-025-00424-1","url":null,"abstract":"The mammary epithelium derives from multipotent mammary stem cells (MaSCs) that engage into differentiation during embryonic development. However, adult MaSCs maintain the ability to reactivate multipotency in non-physiological contexts. We previously reported that Notch1 activation in committed basal cells triggers a basal-to-luminal cell fate switch in the mouse mammary gland. Here, we report conservation of this mechanism and found that in addition to the mammary gland, constitutive Notch1 signaling induces a basal-to-luminal cell fate switch in adult cells of the lacrimal gland, the salivary gland, and the prostate. Since the lineage transition is progressive in time, we performed single-cell transcriptomic analysis on index-sorted mammary cells at different stages of lineage conversion, generating a temporal map of changes in cell identity. Combining single-cell analyses with organoid assays, we demonstrate that cell proliferation is indispensable for this lineage conversion. We also reveal the individual transcriptional landscapes underlying the cellular plasticity switching of committed mammary cells in vivo with spatial and temporal resolution. Given the roles of Notch signaling in cancer, these results may help to better understand the mechanisms that drive cellular transformation.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2827-2855"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789260","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

Structural insights into small-molecule agonist recognition and activation of complement receptor C3aR. 补体受体C3aR的小分子激动剂识别和激活的结构见解。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI: 10.1038/s44318-025-00429-w

Jinuk Kim, Saebom Ko, Chulwon Choi, Jungnam Bae, Hyeonsung Byeon, Chaok Seok, Hee-Jung Choi

{"title":"Structural insights into small-molecule agonist recognition and activation of complement receptor C3aR.","authors":"Jinuk Kim, Saebom Ko, Chulwon Choi, Jungnam Bae, Hyeonsung Byeon, Chaok Seok, Hee-Jung Choi","doi":"10.1038/s44318-025-00429-w","DOIUrl":"10.1038/s44318-025-00429-w","url":null,"abstract":"The complement system plays crucial roles in innate immunity and inflammatory responses. The anaphylatoxin C3a mediates pro-inflammatory and chemotactic functions through the G protein-coupled receptor C3aR. While the active structure of the C3a-C3aR-Gi complex has been determined, the inactive conformation and activation mechanism of C3aR remain elusive. Here we report the cryo-EM structure of ligand-free, G protein-free C3aR, providing insights into its inactive conformation. In addition, we determine the structures of C3aR in complex with the synthetic small-molecule agonist JR14a in two distinct conformational states: a G protein-free intermediate, and a fully active Gi-bound state. The structure of the active JR14a-bound C3aR reveals that JR14a engages in highly conserved interactions with C3aR, similar to the binding of the C-terminal pentapeptide of C3a, along with JR14a-specific interactions. Structural comparison of C3aR in the apo, intermediate, and fully active states provides novel insights into the conformational landscape and activation mechanism of C3aR and defines a molecular basis explaining its high basal activity. Our results may aid in the rational design of therapeutics targeting complement-related inflammatory disorders.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2803-2826"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804558","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

GAF-dependent chromatin plasticity determines promoter usage to mediate locust gregarious behavior. gaf依赖的染色质可塑性决定了启动子的使用，以介导蝗虫的群居行为。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI: 10.1038/s44318-025-00428-x

Xiao Li, Feng Jiang, Qing Liu, Zizheng Zhang, Wenjing Fang, Yutong Wang, Hongran Liu, Le Kang

{"title":"GAF-dependent chromatin plasticity determines promoter usage to mediate locust gregarious behavior.","authors":"Xiao Li, Feng Jiang, Qing Liu, Zizheng Zhang, Wenjing Fang, Yutong Wang, Hongran Liu, Le Kang","doi":"10.1038/s44318-025-00428-x","DOIUrl":"10.1038/s44318-025-00428-x","url":null,"abstract":"Locusts, as devastating pests, can reversibly transform between solitary individuals and gregarious swarms with markedly different behaviors. Epigenetic regulation orchestrated by changes in chromatin openness modulates behavioral plasticity by controlling gene expression. However, the gene regulation mechanisms by which chromatin openness controls behavioral changes remain largely unknown. Here, we explored the regulatory function of chromatin openness in modulating behavioral plasticity, in which the remodeler GAF regulated brain-specific promoter usage in locusts. The increased chromatin openness in gregarious locusts initiated transcription of the brain-specific promoter of henna, a critical gene in dopamine synthesis and gregarious behavior mediation. Furthermore, GAF-dependent chromatin openness responded coordinately to population density changes. Fragment mutagenesis abolished henna promoter activity due to the dysfunction of the GAF-binding site. Mechanistically, the three GAF-binding sites played a synergetic role in remodeling chromatin openness and activating transcription initiation. Our study reveals a novel epigenetic mechanism linking chromatin regulation with behavioral polyphenism in insects during environmental changes.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2928-2948"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804580","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

Author Correction: Toxin-mediated depletion of NAD and NADP drives persister formation in a human pathogen. 作者更正：毒素介导的NAD和NADP的消耗驱动人类病原体的持久性形成。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 DOI: 10.1038/s44318-024-00354-4

Isabella Santi, Raphael Dias Teixeira, Pablo Manfredi, Hector Hernandez Gonzalez, Daniel C Spiess, Guillaume Mas, Alexander Klotz, Andreas Kaczmarczyk, Simon van Vliet, Nicola Zamboni, Sebastian Hiller, Urs Jenal

引用次数: 0

An asymmetric nautilus-like HflK/C assembly controls FtsH proteolysis of membrane proteins. 不对称的鹦鹉螺样HflK/C组装控制FtsH蛋白水解膜蛋白。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-03-13 DOI: 10.1038/s44318-025-00408-1

Alireza Ghanbarpour, Bertina Telusma, Barrett M Powell, Jia Jia Zhang, Isabella Bolstad, Carolyn Vargas, Sandro Keller, Tania A Baker, Robert T Sauer, Joseph H Davis

{"title":"An asymmetric nautilus-like HflK/C assembly controls FtsH proteolysis of membrane proteins.","authors":"Alireza Ghanbarpour, Bertina Telusma, Barrett M Powell, Jia Jia Zhang, Isabella Bolstad, Carolyn Vargas, Sandro Keller, Tania A Baker, Robert T Sauer, Joseph H Davis","doi":"10.1038/s44318-025-00408-1","DOIUrl":"10.1038/s44318-025-00408-1","url":null,"abstract":"The AAA protease FtsH associates with HflK/C subunits to form a megadalton-size complex that spans the inner membrane and extends into the periplasm of E. coli. How this bacterial complex and homologous assemblies in eukaryotic organelles recruit, extract, and degrade membrane-embedded substrates is unclear. Following the overproduction of protein components, recent cryo-EM structures showed symmetric HflK/C cages surrounding FtsH in a manner proposed to inhibit the degradation of membrane-embedded substrates. Here, we present structures of native protein complexes, in which HflK/C instead forms an asymmetric nautilus-shaped assembly with an entryway for membrane-embedded substrates to reach and be engaged by FtsH. Consistent with this nautilus-like structure, proteomic assays suggest that HflK/C enhances FtsH degradation of certain membrane-embedded substrates. Membrane curvature in our FtsH•HflK/C complexes is opposite that of surrounding membrane regions, a property that correlates with lipid scramblase activity and possibly with FtsH's function in the degradation of membrane-embedded proteins.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2501-2513"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626663","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

A versatile toolbox for determining IRES activity in cells and embryonic tissues. 用于测定细胞和胚胎组织中IRES活性的多功能工具箱。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-03-13 DOI: 10.1038/s44318-025-00404-5

Philipp Koch, Zijian Zhang, Naomi R Genuth, Teodorus Theo Susanto, Martin Haimann, Alena Khmelinskaia, Gun Woo Byeon, Saurabh Dey, Maria Barna, Kathrin Leppek

{"title":"A versatile toolbox for determining IRES activity in cells and embryonic tissues.","authors":"Philipp Koch, Zijian Zhang, Naomi R Genuth, Teodorus Theo Susanto, Martin Haimann, Alena Khmelinskaia, Gun Woo Byeon, Saurabh Dey, Maria Barna, Kathrin Leppek","doi":"10.1038/s44318-025-00404-5","DOIUrl":"10.1038/s44318-025-00404-5","url":null,"abstract":"Widespread control of gene expression through translation has emerged as a key level of spatiotemporal regulation of protein expression. A prominent mechanism by which ribosomes can confer gene regulation is via internal ribosomal entry sites (IRESes), whose functions have however, remained difficult to rigorously characterize. Here we present a set of technologies in embryos and cells, including IRES-mediated translation of circular RNA (circRNA) reporters, single-molecule messenger (m)RNA isoform imaging, PacBio long-read sequencing, and isoform-sensitive mRNA quantification along polysome profiles as a new toolbox for understanding IRES regulation. Using these techniques, we investigate a broad range of cellular IRES RNA elements including Hox IRESes. We show IRES-dependent translation in circRNAs, as well as the relative expression, localization, and translation of an IRES-containing mRNA isoform in specific embryonic tissues. We thereby provide a new resource of technologies to elucidate the roles of versatile IRES elements in gene regulation and embryonic development.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2695-2724"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626659","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