The EMBO Journal最新文献_第5页

O-GlcNAcylation of circadian clock protein Bmal1 impairs cognitive function in diabetic mice. 昼夜节律钟蛋白 Bmal1 的 O-GlcNAcylation 会损害糖尿病小鼠的认知功能。

The EMBO Journal Pub Date : 2024-10-07 DOI: 10.1038/s44318-024-00263-6

Ya Hui,Yuanmei Zhong,Liuyu Kuang,Jingxi Xu,Yuqi Hao,Jingxue Cao,Tianpeng Zheng

引用次数: 0

Alternative splicing of PBRM1 mediates resistance to PD-1 blockade therapy in renal cancer. PBRM1的替代剪接介导了肾癌患者对PD-1阻断疗法的耐受性。

The EMBO Journal Pub Date : 2024-10-07 DOI: 10.1038/s44318-024-00262-7

Namjoon Cho,Seung-Yeon Kim,Sung-Gwon Lee,Chungoo Park,Sunkyung Choi,Eun-Mi Kim,Kee K Kim

引用次数: 0

PIWI-interacting RNAs: who, what, when, where, why, and how. 与 PIWI 相互作用的 RNA：谁、什么、何时、何地、为何以及如何作用。

The EMBO Journal Pub Date : 2024-09-26 DOI: 10.1038/s44318-024-00253-8

Astrid D Haase,Rene F Ketting,Eric C Lai,Ronald P van Rij,Mikiko Siomi,Petr Svoboda,Josien C van Wolfswinkel,Pei-Hsuan Wu

引用次数: 0

CEP192 localises mitotic Aurora-A activity by priming its interaction with TPX2. CEP192 通过启动有丝分裂 Aurora-A 与 TPX2 的相互作用，定位 Aurora-A 的活性。

The EMBO Journal Pub Date : 2024-09-26 DOI: 10.1038/s44318-024-00240-z

James Holder,Jennifer A Miles,Matthew Batchelor,Harrison Popple,Martin Walko,Wayland Yeung,Natarajan Kannan,Andrew J Wilson,Richard Bayliss,Fanni Gergely

{"title":"CEP192 localises mitotic Aurora-A activity by priming its interaction with TPX2.","authors":"James Holder,Jennifer A Miles,Matthew Batchelor,Harrison Popple,Martin Walko,Wayland Yeung,Natarajan Kannan,Andrew J Wilson,Richard Bayliss,Fanni Gergely","doi":"10.1038/s44318-024-00240-z","DOIUrl":"https://doi.org/10.1038/s44318-024-00240-z","url":null,"abstract":"Aurora-A is an essential cell-cycle kinase with critical roles in mitotic entry and spindle dynamics. These functions require binding partners such as CEP192 and TPX2, which modulate both kinase activity and localisation of Aurora-A. Here we investigate the structure and role of the centrosomal Aurora-A:CEP192 complex in the wider molecular network. We find that CEP192 wraps around Aurora-A, occupies the binding sites for mitotic spindle-associated partners, and thus competes with them. Comparison of two different Aurora-A conformations reveals how CEP192 modifies kinase activity through the site used for TPX2-mediated activation. Deleting the Aurora-A-binding interface in CEP192 prevents centrosomal accumulation of Aurora-A, curtails its activation-loop phosphorylation, and reduces spindle-bound TPX2:Aurora-A complexes, resulting in error-prone mitosis. Thus, by supplying the pool of phosphorylated Aurora-A necessary for TPX2 binding, CEP192:Aurora-A complexes regulate spindle function. We propose an evolutionarily conserved spatial hierarchy, which protects genome integrity through fine-tuning and correctly localising Aurora-A activity.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328986","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

RNA degradation triggered by decapping is largely independent of initial deadenylation. 脱帽引发的 RNA 降解在很大程度上与最初的去淀粉化无关。

The EMBO Journal Pub Date : 2024-09-25 DOI: 10.1038/s44318-024-00250-x

Léna Audebert,Frank Feuerbach,Mostafa Zedan,Alexandra P Schürch,Laurence Decourty,Abdelkader Namane,Emmanuelle Permal,Karsten Weis,Gwenaël Badis,Cosmin Saveanu

{"title":"RNA degradation triggered by decapping is largely independent of initial deadenylation.","authors":"Léna Audebert,Frank Feuerbach,Mostafa Zedan,Alexandra P Schürch,Laurence Decourty,Abdelkader Namane,Emmanuelle Permal,Karsten Weis,Gwenaël Badis,Cosmin Saveanu","doi":"10.1038/s44318-024-00250-x","DOIUrl":"https://doi.org/10.1038/s44318-024-00250-x","url":null,"abstract":"RNA stability, important for eukaryotic gene expression, is thought to depend on deadenylation rates, with shortened poly(A) tails triggering decapping and 5' to 3' degradation. In contrast to this view, recent large-scale studies indicate that the most unstable mRNAs have, on average, long poly(A) tails. To clarify the role of deadenylation in mRNA decay, we first modeled mRNA poly(A) tail kinetics and mRNA stability in yeast. Independent of deadenylation rates, differences in mRNA decapping rates alone were sufficient to explain current large-scale results. To test the hypothesis that deadenylation and decapping are uncoupled, we used rapid depletion of decapping and deadenylation enzymes and measured changes in mRNA levels, poly(A) length and stability, both transcriptome-wide and with individual reporters. These experiments revealed that perturbations in poly(A) tail length did not correlate with variations in mRNA stability. Thus, while deadenylation may be critical for specific regulatory mechanisms, our results suggest that for most yeast mRNAs, it is not critical for mRNA decapping and degradation.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"217 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325035","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

Author Correction: PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation. 作者更正：PARP14和PARP9/DTX3L调控干扰素诱导的ADP-核糖基化。

The EMBO Journal Pub Date : 2024-09-25 DOI: 10.1038/s44318-024-00247-6

Pulak Kar,Chatrin Chatrin,Nina Đukić,Osamu Suyari,Marion Schuller,Kang Zhu,Evgeniia Prokhorova,Nicolas Bigot,Domagoj Baretić,Juraj Ahel,Jonas Damgaard Elsborg,Michael L Nielsen,Tim Clausen,Sébastien Huet,Mario Niepel,Sumana Sanyal,Dragana Ahel,Rebecca Smith,Ivan Ahel

引用次数: 0

m6A mRNA methylation by METTL14 regulates early pancreatic cell differentiation. METTL14 的 m6A mRNA 甲基化调控早期胰腺细胞分化。

The EMBO Journal Pub Date : 2024-09-25 DOI: 10.1038/s44318-024-00213-2

Sevim Kahraman,Dario F De Jesus,Jiangbo Wei,Natalie K Brown,Zhongyu Zou,Jiang Hu,Mehdi Pirouz,Richard I Gregory,Chuan He,Rohit N Kulkarni

引用次数: 0

Toxin-mediated depletion of NAD and NADP drives persister formation in a human pathogen. 毒素介导的 NAD 和 NADP 消耗促使一种人类病原体形成顽固病菌。

The EMBO Journal Pub Date : 2024-09-25 DOI: 10.1038/s44318-024-00248-5

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

{"title":"Toxin-mediated depletion of NAD and NADP drives persister formation in a human pathogen.","authors":"Isabella Santi,Raphael Dias Teixeira,Pablo Manfredi,Hector Hernandez Gonzalez,Daniel C Spiess,Guillaume Mas,Alexander Klotz,Andreas Kaczmarczyk,Nicola Zamboni,Sebastian Hiller,Urs Jenal","doi":"10.1038/s44318-024-00248-5","DOIUrl":"https://doi.org/10.1038/s44318-024-00248-5","url":null,"abstract":"Toxin-antitoxin (TA) systems are widespread in bacteria and implicated in genome stability, virulence, phage defense, and persistence. TA systems have diverse activities and cellular targets, but their physiological roles and regulatory mechanisms are often unclear. Here, we show that the NatR-NatT TA system, which is part of the core genome of the human pathogen Pseudomonas aeruginosa, generates drug-tolerant persisters by specifically depleting nicotinamide dinucleotides. While actively growing P. aeruginosa cells compensate for NatT-mediated NAD+ deficiency by inducing the NAD+ salvage pathway, NAD depletion generates drug-tolerant persisters under nutrient-limited conditions. Our structural and biochemical analyses propose a model for NatT toxin activation and autoregulation and indicate that NatT activity is subject to powerful metabolic feedback control by the NAD+ precursor nicotinamide. Based on the identification of natT gain-of-function alleles in patient isolates and on the observation that NatT increases P. aeruginosa virulence, we postulate that NatT modulates pathogen fitness during infections. These findings pave the way for detailed investigations into how a toxin-antitoxin system can promote pathogen persistence by disrupting essential metabolic pathways.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325034","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

BATokines in metabolic liver disease: good cops or bad cops? 代谢性肝病中的 BATokines：好警察还是坏警察？

The EMBO Journal Pub Date : 2024-09-25 DOI: 10.1038/s44318-024-00239-6

Renata O Pereira,E Dale Abel

引用次数: 0

miRNA-mediated gene silencing in Drosophila larval development involves GW182-dependent and independent mechanisms. 果蝇幼虫发育过程中 miRNA 介导的基因沉默涉及 GW182 依赖性和独立机制。

The EMBO Journal Pub Date : 2024-09-25 DOI: 10.1038/s44318-024-00249-4

Eriko Matsuura-Suzuki,Kaori Kiyokawa,Shintaro Iwasaki,Yukihide Tomari

{"title":"miRNA-mediated gene silencing in Drosophila larval development involves GW182-dependent and independent mechanisms.","authors":"Eriko Matsuura-Suzuki,Kaori Kiyokawa,Shintaro Iwasaki,Yukihide Tomari","doi":"10.1038/s44318-024-00249-4","DOIUrl":"https://doi.org/10.1038/s44318-024-00249-4","url":null,"abstract":"MicroRNAs (miRNAs) regulate a wide variety of biological processes by silencing their target genes. Argonaute (AGO) proteins load miRNAs to form an RNA-induced silencing complex (RISC), which mediates translational repression and/or mRNA decay of the targets. A scaffold protein called GW182 directly binds AGO and the CCR4-NOT deadenylase complex, initiating the mRNA decay reaction. Although previous studies have demonstrated the critical role of GW182 in cultured cells as well as in cell-free systems, its biological significance in living organisms remains poorly explored, especially in Drosophila melanogaster. Here, we generated gw182-null flies using the CRISPR/Cas9 system and found that, unexpectedly, they can survive until an early second-instar larval stage. Moreover, in vivo miRNA reporters can be effectively repressed in gw182-null first-instar larvae. Nevertheless, gw182-null flies have defects in the expression of chitin-related genes and the formation of the larval trachea system, preventing them from completing larval development. Our results highlight the importance of both GW182-dependent and -independent silencing mechanisms in vivo.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325123","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