EMBO Journal最新文献_第10页

PQBP3 prevents senescence by suppressing PSME3-mediated proteasomal Lamin B1 degradation. PQBP3 通过抑制 PSME3 介导的蛋白酶体 Lamin B1 降解来防止衰老。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-09-01 Epub Date: 2024-08-05 DOI: 10.1038/s44318-024-00192-4

Yuki Yoshioka, Yong Huang, Xiaocen Jin, Kien Xuan Ngo, Tomohiro Kumaki, Meihua Jin, Saori Toyoda, Sumire Takayama, Maiko Inotsume, Kyota Fujita, Hidenori Homma, Toshio Ando, Hikari Tanaka, Hitoshi Okazawa

{"title":"PQBP3 prevents senescence by suppressing PSME3-mediated proteasomal Lamin B1 degradation.","authors":"Yuki Yoshioka, Yong Huang, Xiaocen Jin, Kien Xuan Ngo, Tomohiro Kumaki, Meihua Jin, Saori Toyoda, Sumire Takayama, Maiko Inotsume, Kyota Fujita, Hidenori Homma, Toshio Ando, Hikari Tanaka, Hitoshi Okazawa","doi":"10.1038/s44318-024-00192-4","DOIUrl":"10.1038/s44318-024-00192-4","url":null,"abstract":"Senescence of nondividing neurons remains an immature concept, with especially the regulatory molecular mechanisms of senescence-like phenotypes and the role of proteins associated with neurodegenerative diseases in triggering neuronal senescence remaining poorly explored. In this study, we reveal that the nucleolar polyglutamine binding protein 3 (PQBP3; also termed NOL7), which has been linked to polyQ neurodegenerative diseases, regulates senescence as a gatekeeper of cytoplasmic DNA leakage. PQBP3 directly binds PSME3 (proteasome activator complex subunit 3), a subunit of the 11S proteasome regulator complex, decreasing PSME3 interaction with Lamin B1 and thereby preventing Lamin B1 degradation and senescence. Depletion of endogenous PQBP3 causes nuclear membrane instability and release of genomic DNA from the nucleus to the cytosol. Among multiple tested polyQ proteins, ataxin-1 (ATXN1) partially sequesters PQBP3 to inclusion bodies, reducing nucleolar PQBP3 levels. Consistently, knock-in mice expressing mutant Atxn1 exhibit decreased nuclear PQBP3 and a senescence phenotype in Purkinje cells of the cerebellum. Collectively, these results suggest homologous roles of the nucleolar protein PQBP3 in cellular senescence and neurodegeneration.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"3968-3999"},"PeriodicalIF":9.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894803","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 viral effector blocks the turnover of a plant NLR receptor to trigger a robust immune response. 一种病毒效应物阻断了植物 NLR 受体的转换，从而引发强大的免疫反应。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-09-01 Epub Date: 2024-07-17 DOI: 10.1038/s44318-024-00174-6

Chunli Wang, Min Zhu, Hao Hong, Jia Li, Chongkun Zuo, Yu Zhang, Yajie Shi, Suyu Liu, Haohua Yu, Yuling Yan, Jing Chen, Lingna Shangguan, Aiping Zhi, Rongzhen Chen, Karen Thulasi Devendrakumar, Xiaorong Tao

{"title":"A viral effector blocks the turnover of a plant NLR receptor to trigger a robust immune response.","authors":"Chunli Wang, Min Zhu, Hao Hong, Jia Li, Chongkun Zuo, Yu Zhang, Yajie Shi, Suyu Liu, Haohua Yu, Yuling Yan, Jing Chen, Lingna Shangguan, Aiping Zhi, Rongzhen Chen, Karen Thulasi Devendrakumar, Xiaorong Tao","doi":"10.1038/s44318-024-00174-6","DOIUrl":"10.1038/s44318-024-00174-6","url":null,"abstract":"Plant intracellular nucleotide-binding and leucine-rich repeat immune receptors (NLRs) play a key role in activating a strong pathogen defense response. Plant NLR proteins are tightly regulated and accumulate at very low levels in the absence of pathogen effectors. However, little is known about how this low level of NLR proteins is able to induce robust immune responses upon recognition of pathogen effectors. Here, we report that, in the absence of effector, the inactive form of the tomato NLR Sw-5b is targeted for ubiquitination by the E3 ligase SBP1. Interaction of SBP1 with Sw-5b via only its N-terminal domain leads to slow turnover. In contrast, in its auto-active state, Sw-5b is rapidly turned over as SBP1 is upregulated and interacts with both its N-terminal and NB-LRR domains. During infection with the tomato spotted wilt virus, the viral effector NSm interacts with Sw-5b and disrupts the interaction of Sw-5b with SBP1, thereby stabilizing the active Sw-5b and allowing it to induce a robust immune response.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"3650-3676"},"PeriodicalIF":9.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635647","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

Germline loss in C. elegans enhances longevity by disrupting adhesion between niche and stem cells. 秀丽隐杆线虫的种系缺失会破坏龛位细胞和干细胞之间的粘附，从而延长寿命。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-09-01 Epub Date: 2024-07-25 DOI: 10.1038/s44318-024-00185-3

Meng Liu, Jiehui Chen, Guizhong Cui, Yumin Dai, Mengjiao Song, Chunyu Zhou, Qingyuan Hu, Qingxia Chen, Hongwei Wang, Wanli Chen, Jingdong Jackie Han, Guangdun Peng, Naihe Jing, Yidong Shen

{"title":"Germline loss in C. elegans enhances longevity by disrupting adhesion between niche and stem cells.","authors":"Meng Liu, Jiehui Chen, Guizhong Cui, Yumin Dai, Mengjiao Song, Chunyu Zhou, Qingyuan Hu, Qingxia Chen, Hongwei Wang, Wanli Chen, Jingdong Jackie Han, Guangdun Peng, Naihe Jing, Yidong Shen","doi":"10.1038/s44318-024-00185-3","DOIUrl":"10.1038/s44318-024-00185-3","url":null,"abstract":"Ageing and fertility are intertwined. Germline loss extends the lifespan in various organisms, termed gonadal longevity. However, the original longevity signal from the somatic gonad remains poorly understood. Here, we focused on the interaction between germline stem cells (GSCs) and their niche, the distal tip cells (DTCs), to explore the barely known longevity signal from the somatic gonad in C. elegans. We found that removing germline disrupts the cell adhesions between GSC and DTC, causing a significant transcriptomic change in DTC through hmp-2/β-catenin and two GATA transcription factors, elt-3 and pqm-1 in this niche cell. Inhibiting elt-3 and pqm-1 in DTC suppresses gonadal longevity. Moreover, we further identified the TGF-β ligand, tig-2, as the cytokine from DTC upon the loss of germline, which evokes the downstream gonadal longevity signalling throughout the body. Our findings thus reveal the source of the longevity signalling in response to germline removal, highlighting the stem cell niche as a critical signalling hub in ageing.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"4000-4019"},"PeriodicalIF":9.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767998","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

Neutral evolution of snoRNA Host Gene long non-coding RNA affects cell fate control. snoRNA 的中性进化宿主基因长非编码 RNA 影响细胞命运控制

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-09-01 Epub Date: 2024-07-25 DOI: 10.1038/s44318-024-00172-8

Matteo Vietri Rudan, Kalle H Sipilä, Christina Philippeos, Clarisse Ganier, Priyanka G Bhosale, Victor A Negri, Fiona M Watt

{"title":"Neutral evolution of snoRNA Host Gene long non-coding RNA affects cell fate control.","authors":"Matteo Vietri Rudan, Kalle H Sipilä, Christina Philippeos, Clarisse Ganier, Priyanka G Bhosale, Victor A Negri, Fiona M Watt","doi":"10.1038/s44318-024-00172-8","DOIUrl":"10.1038/s44318-024-00172-8","url":null,"abstract":"A fundamental challenge in molecular biology is to understand how evolving genomes can acquire new functions. Actively transcribed, non-coding parts of the genome provide a potential platform for the development of new functional sequences, but their biological and evolutionary roles remain largely unexplored. Here, we show that a set of neutrally evolving long non-coding RNAs (lncRNAs) whose introns encode small nucleolar RNAs (snoRNA Host Genes, SNHGs) are highly expressed in skin and dysregulated in inflammatory conditions. Using SNHG7 and human epidermal keratinocytes as a model, we describe a mechanism by which these lncRNAs can increase self-renewal and inhibit differentiation. The activity of SNHG7 lncRNA has been recently acquired in the primate lineage and depends on a short sequence required for microRNA binding. Taken together, our results highlight the importance of understanding the role of fast-evolving transcripts in normal and diseased epithelia, and show how poorly conserved, actively transcribed non-coding sequences can participate in the evolution of genomic functionality.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"4049-4067"},"PeriodicalIF":9.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762344","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

Non-canonical NF-κB signaling limits the tolerogenic β-catenin-Raldh2 axis in gut dendritic cells to exacerbate intestinal pathologies. 非典型的 NF-κB 信号限制了肠道树突状细胞中具有耐受性的β-catenin-Raldh2 轴，从而加剧了肠道病变。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-09-01 Epub Date: 2024-07-25 DOI: 10.1038/s44318-024-00182-6

Alvina Deka, Naveen Kumar, Swapnava Basu, Meenakshi Chawla, Namrata Bhattacharya, Sk Asif Ali, Bhawna, Upasna Madan, Shakti Kumar, Bhabatosh Das, Debarka Sengupta, Amit Awasthi, Soumen Basak

{"title":"Non-canonical NF-κB signaling limits the tolerogenic β-catenin-Raldh2 axis in gut dendritic cells to exacerbate intestinal pathologies.","authors":"Alvina Deka, Naveen Kumar, Swapnava Basu, Meenakshi Chawla, Namrata Bhattacharya, Sk Asif Ali, Bhawna, Upasna Madan, Shakti Kumar, Bhabatosh Das, Debarka Sengupta, Amit Awasthi, Soumen Basak","doi":"10.1038/s44318-024-00182-6","DOIUrl":"10.1038/s44318-024-00182-6","url":null,"abstract":"Dendritic cell (DC) dysfunction is known to exacerbate intestinal pathologies, but the mechanisms compromising DC-mediated immune regulation in this context remain unclear. Here, we show that intestinal dendritic cells from a mouse model of experimental colitis exhibit significant levels of noncanonical NF-κB signaling, which activates the RelB:p52 heterodimer. Genetic inactivation of this pathway in DCs alleviates intestinal pathologies in mice suffering from colitis. Deficiency of RelB:p52 diminishes transcription of Axin1, a critical component of the β-catenin destruction complex, reinforcing β-catenin-dependent expression of Raldh2, which imparts tolerogenic DC attributes by promoting retinoic acid synthesis. DC-specific impairment of noncanonical NF-κB signaling leads to increased colonic numbers of Tregs and IgA+ B cells, which promote luminal IgA production and foster eubiosis. Experimentally introduced β-catenin haploinsufficiency in DCs with deficient noncanonical NF-κB signaling moderates Raldh2 activity, reinstating colitogenic sensitivity in mice. Finally, inflammatory bowel-disease patients also display a deleterious noncanonical NF-κB signaling signature in intestinal DCs. In sum, we establish how noncanonical NF-κB signaling in dendritic cells can subvert retinoic acid synthesis to fuel intestinal inflammation.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"3895-3915"},"PeriodicalIF":9.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767999","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

RNA helicase SKIV2L limits antiviral defense and autoinflammation elicited by the OAS-RNase L pathway. RNA 螺旋酶 SKIV2L 限制了 OAS-RNase L 途径引起的抗病毒防御和自身炎症。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-09-01 Epub Date: 2024-08-07 DOI: 10.1038/s44318-024-00187-1

Kun Yang, Beihua Dong, Abhishek Asthana, Robert H Silverman, Nan Yan

{"title":"RNA helicase SKIV2L limits antiviral defense and autoinflammation elicited by the OAS-RNase L pathway.","authors":"Kun Yang, Beihua Dong, Abhishek Asthana, Robert H Silverman, Nan Yan","doi":"10.1038/s44318-024-00187-1","DOIUrl":"10.1038/s44318-024-00187-1","url":null,"abstract":"The OAS-RNase L pathway is one of the oldest innate RNA sensing pathways that leads to interferon (IFN) signaling and cell death. OAS recognizes viral RNA and then activates RNase L, which subsequently cleaves both cellular and viral RNA, creating \"processed RNA\" as an endogenous ligand that further triggers RIG-I-like receptor signaling. However, the IFN response and antiviral activity of the OAS-RNase L pathway are weak compared to other RNA-sensing pathways. Here, we discover that the SKIV2L RNA exosome limits the antiviral capacity of the OAS-RNase L pathway. SKIV2L-deficient cells exhibit remarkably increased interferon responses to RNase L-processed RNA, resulting in heightened antiviral activity. The helicase activity of SKIV2L is indispensable for this function, acting downstream of RNase L. SKIV2L depletion increases the antiviral capacity of OAS-RNase L against RNA virus infection. Furthermore, SKIV2L loss exacerbates autoinflammation caused by human OAS1 gain-of-function mutations. Taken together, our results identify SKIV2L as a critical barrier to OAS-RNase L-mediated antiviral immunity that could be therapeutically targeted to enhance the activity of a basic antiviral pathway.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"3876-3894"},"PeriodicalIF":9.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903459","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

LINE1 and its host: one cell's junk is another cell's treasure. LINE1 及其宿主：一个细胞的垃圾是另一个细胞的宝藏。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-09-01 Epub Date: 2024-07-29 DOI: 10.1038/s44318-024-00175-5

John C Martinez, Andrei Seluanov, Vera Gorbunova

引用次数: 0

DNA replication recruits a friend to overcome a challenging break-up. DNA 复制招募了一位朋友来克服分手的挑战。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-09-01 Epub Date: 2024-08-21 DOI: 10.1038/s44318-024-00204-3

James M Dewar

引用次数: 0

Deubiquitinating enzyme mutagenesis screens identify a USP43-dependent HIF-1 transcriptional response. 去泛素化酶诱变筛选确定了一种依赖于 USP43 的 HIF-1 转录反应。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-09-01 Epub Date: 2024-07-15 DOI: 10.1038/s44318-024-00166-6

Tekle Pauzaite, Niek Wit, Rachel V Seear, James A Nathan

引用次数: 0

Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification. 黑色素瘤分泌的黑色素小体可调节肿瘤相关巨噬细胞的多样化。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2024-09-01 Epub Date: 2024-05-08 DOI: 10.1038/s44318-024-00103-7

Roma Parikh, Shivang Parikh, Daniella Berzin, Hananya Vaknine, Shai Ovadia, Daniela Likonen, Shoshana Greenberger, Alon Scope, Sharona Elgavish, Yuval Nevo, Inbar Plaschkes, Eran Nizri, Oren Kobiler, Avishai Maliah, Laureen Zaremba, Vishnu Mohan, Irit Sagi, Ruth Ashery-Padan, Yaron Carmi, Chen Luxenburg, Jörg D Hoheisel, Mehdi Khaled, Mitchell P Levesque, Carmit Levy

{"title":"Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification.","authors":"Roma Parikh, Shivang Parikh, Daniella Berzin, Hananya Vaknine, Shai Ovadia, Daniela Likonen, Shoshana Greenberger, Alon Scope, Sharona Elgavish, Yuval Nevo, Inbar Plaschkes, Eran Nizri, Oren Kobiler, Avishai Maliah, Laureen Zaremba, Vishnu Mohan, Irit Sagi, Ruth Ashery-Padan, Yaron Carmi, Chen Luxenburg, Jörg D Hoheisel, Mehdi Khaled, Mitchell P Levesque, Carmit Levy","doi":"10.1038/s44318-024-00103-7","DOIUrl":"10.1038/s44318-024-00103-7","url":null,"abstract":"Extracellular vesicles (EVs) are important mediators of communication between cells. Here, we reveal a new mode of intercellular communication by melanosomes, large EVs secreted by melanocytes for melanin transport. Unlike small EVs, which are disintegrated within the receiver cell, melanosomes stay intact within them, gain a unique protein signature, and can then be further transferred to another cell as \"second-hand\" EVs. We show that melanoma-secreted melanosomes passaged through epidermal keratinocytes or dermal fibroblasts can be further engulfed by resident macrophages. This process leads to macrophage polarization into pro-tumor or pro-immune cell infiltration phenotypes. Melanosomes that are transferred through fibroblasts can carry AKT1, which induces VEGF secretion from macrophages in an mTOR-dependent manner, promoting angiogenesis and metastasis in vivo. In melanoma patients, macrophages that are co-localized with AKT1 are correlated with disease aggressiveness, and immunotherapy non-responders are enriched in macrophages containing melanosome markers. Our findings suggest that interactions mediated by second-hand extracellular vesicles contribute to the formation of the metastatic niche, and that blocking the melanosome cues of macrophage diversification could be helpful in halting melanoma progression.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"3553-3586"},"PeriodicalIF":9.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892850","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