EMBO Reports最新文献_第9页

Regulating translation in aging: from global to gene-specific mechanisms. 衰老过程中的翻译调控：从全球机制到基因特异性机制。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-12-01 Epub Date: 2024-11-19 DOI: 10.1038/s44319-024-00315-2

Mathilde Solyga, Amitabha Majumdar, Florence Besse

{"title":"Regulating translation in aging: from global to gene-specific mechanisms.","authors":"Mathilde Solyga, Amitabha Majumdar, Florence Besse","doi":"10.1038/s44319-024-00315-2","DOIUrl":"10.1038/s44319-024-00315-2","url":null,"abstract":"Aging is characterized by a decline in various biological functions that is associated with changes in gene expression programs. Recent transcriptome-wide integrative studies in diverse organisms and tissues have revealed a gradual uncoupling between RNA and protein levels with aging, which highlights the importance of post-transcriptional regulatory processes. Here, we provide an overview of multi-omics analyses that show the progressive uncorrelation of transcriptomes and proteomes during the course of healthy aging. We then describe the molecular changes leading to global downregulation of protein synthesis with age and review recent work dissecting the mechanisms involved in gene-specific translational regulation in complementary model organisms. These mechanisms include the recognition of regulated mRNAs by trans-acting factors such as miRNA and RNA-binding proteins, the condensation of mRNAs into repressive cytoplasmic RNP granules, and the pausing of ribosomes at specific residues. Lastly, we mention future challenges of this emerging field, possible buffering functions as well as potential links with disease.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"5265-5276"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675463","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 binding protein ZCCHC24 promotes tumorigenicity in triple-negative breast cancer. RNA 结合蛋白 ZCCHC24 促进了三阴性乳腺癌的致瘤性。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-12-01 Epub Date: 2024-10-17 DOI: 10.1038/s44319-024-00282-8

Yutaro Uchida, Ryota Kurimoto, Tomoki Chiba, Takahide Matsushima, Goshi Oda, Iichiroh Onishi, Yasuto Takeuchi, Noriko Gotoh, Hiroshi Asahara

{"title":"RNA binding protein ZCCHC24 promotes tumorigenicity in triple-negative breast cancer.","authors":"Yutaro Uchida, Ryota Kurimoto, Tomoki Chiba, Takahide Matsushima, Goshi Oda, Iichiroh Onishi, Yasuto Takeuchi, Noriko Gotoh, Hiroshi Asahara","doi":"10.1038/s44319-024-00282-8","DOIUrl":"10.1038/s44319-024-00282-8","url":null,"abstract":"Triple-negative breast cancer (TNBC) lacks the expression of hormone and HER2 receptors and is highly malignant with no effective therapeutic targets. In TNBC, the cancer stem-like cell (CSC) population is considered to be the main cause of resistance to treatment. Thus, the therapeutic targeting of this population could substantially improve patient survival. Here, we identify the RNA-binding protein ZCCHC24 as enriched in the mesenchymal-like TNBC population. ZCCHC24 promotes the expression of a set of genes related to tumorigenicity and treatment resistance by directly binding to the cis-element \"UGUWHWWA\" in their mRNAs, thereby stabilizing them. One of the ZCCHC24 targets, ZEB1, is a transcription factor that promotes the expression of cancer stemness genes and reciprocally induces ZCCHC24 expression. ZCCHC24 knockdown by siRNAs shows a therapeutic effect and reduces the mesenchymal-like cell population in TNBC patient-derived xenografts. ZCCHC24 knockdown also has additive effects with the BET inhibitor JQ1 in suppressing tumor growth in TNBC patient-derived xenografts.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"5352-5382"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460725","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

Gpr54 deletion accelerates hair cycle and hair regeneration. Gpr54 基因缺失可加速毛发周期和毛发再生。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-25 DOI: 10.1038/s44319-024-00327-y

Weili Xia, Caibing Wang, Biao Guo, Zexin Tang, Xiyun Ye, Yongyan Dang

{"title":"Gpr54 deletion accelerates hair cycle and hair regeneration.","authors":"Weili Xia, Caibing Wang, Biao Guo, Zexin Tang, Xiyun Ye, Yongyan Dang","doi":"10.1038/s44319-024-00327-y","DOIUrl":"https://doi.org/10.1038/s44319-024-00327-y","url":null,"abstract":"GPR54, or KiSS-1R (Kisspeptin receptor), is key in puberty initiation and tumor metastasis prevention, but its role on hair follicles remains unclear. Our study shows that Gpr54 knockout (KO) accelerates hair cycle, synchronized hair regeneration and transplanted hair growth in mice. In Gpr54 KO mice, DPC (dermal papilla cell) activity is enhanced, with elevated expression of Wnts, VEGF, and IGF-1, which stimulate HFSCs. Gpr54 deletion also raises the number of CD34+ and Lgr5+ HFSCs. The Gpr54 inhibitor, kisspeptin234, promotes hair shaft growth in cultured mouse hair follicles and boosts synchronized hair regeneration in vivo. Mechanistically, Gpr54 deletion suppresses NFATC3 expression in DPCs and HFSCs, and decreases levels of SFRP1, a Wnt inhibitor. It also activates the Wnt/β-catenin pathway, promoting β-catenin nuclear localization and upregulating target genes such as Lef1 and ALP. Our findings suggest that Gpr54 deletion may accelerate the hair cycle and promote hair regeneration in mice by regulating the NAFTc3-SFRP1-Wnt signaling pathway. These findings suggest that Gpr54 could be a possible target for future hair loss treatments.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Dystrophin-Dystroglycan complex ensures cytokinesis efficiency in Drosophila epithelia. Dystrophin-Dystroglycan复合体可确保果蝇上皮细胞的细胞分裂效率。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-15 DOI: 10.1038/s44319-024-00319-y

Margarida Gonçalves, Catarina Lopes, Hervé Alégot, Mariana Osswald, Floris Bosveld, Carolina Ramos, Graziella Richard, Yohanns Bellaiche, Vincent Mirouse, Eurico Morais-de-Sá

{"title":"The Dystrophin-Dystroglycan complex ensures cytokinesis efficiency in Drosophila epithelia.","authors":"Margarida Gonçalves, Catarina Lopes, Hervé Alégot, Mariana Osswald, Floris Bosveld, Carolina Ramos, Graziella Richard, Yohanns Bellaiche, Vincent Mirouse, Eurico Morais-de-Sá","doi":"10.1038/s44319-024-00319-y","DOIUrl":"https://doi.org/10.1038/s44319-024-00319-y","url":null,"abstract":"Cytokinesis physically separates daughter cells at the end of cell division. This step is particularly challenging for epithelial cells, which are connected to their neighbors and to the extracellular matrix by transmembrane protein complexes. To systematically evaluate the impact of the cell adhesion machinery on epithelial cytokinesis efficiency, we performed an RNAi-based modifier screen in the Drosophila follicular epithelium. Strikingly, this unveiled adhesion molecules and transmembrane receptors that facilitate cytokinesis completion. Among these is Dystroglycan, which connects the extracellular matrix to the cytoskeleton via Dystrophin. Live imaging revealed that Dystrophin and Dystroglycan become enriched in the ingressing membrane, below the cytokinetic ring, during and after ring constriction. Using multiple alleles, including Dystrophin isoform-specific mutants, we show that Dystrophin/Dystroglycan localization is linked with unanticipated roles in regulating cytokinetic ring contraction and in preventing membrane regression during the abscission period. Altogether, we provide evidence that, rather than opposing cytokinesis completion, the machinery involved in cell-cell and cell-matrix interactions has also evolved functions to ensure cytokinesis efficiency in epithelial tissues.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dinoflagellate mRNA is pervasively modified with m¹A. 甲藻 mRNA 普遍被 m1A 修饰。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-09-20 DOI: 10.1038/s44319-024-00263-x

Jianheng Fox Liu, Samie R Jaffrey

引用次数: 0

CHK1 controls zygote pronuclear envelope breakdown by regulating F-actin through interacting with MICAL3. CHK1 通过与 MICAL3 相互作用来调节 F-肌动蛋白，从而控制子代原核包膜的破裂。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-10-02 DOI: 10.1038/s44319-024-00267-7

Honghui Zhang, Ying Cui, Bohan Yang, Zhenzhen Hou, Mengge Zhang, Wei Su, Tailai Chen, Yuehong Bian, Mei Li, Zi-Jiang Chen, Han Zhao, Shigang Zhao, Keliang Wu

{"title":"CHK1 controls zygote pronuclear envelope breakdown by regulating F-actin through interacting with MICAL3.","authors":"Honghui Zhang, Ying Cui, Bohan Yang, Zhenzhen Hou, Mengge Zhang, Wei Su, Tailai Chen, Yuehong Bian, Mei Li, Zi-Jiang Chen, Han Zhao, Shigang Zhao, Keliang Wu","doi":"10.1038/s44319-024-00267-7","DOIUrl":"10.1038/s44319-024-00267-7","url":null,"abstract":"CHK1 mutations could cause human zygote arrest at the pronuclei stage, a phenomenon that is not well understood at the molecular level. In this study, we conducted experiments where pre-pronuclei from zygotes with CHK1 mutation were transferred into the cytoplasm of normal enucleated fertilized eggs. This approach rescued the zygote arrest caused by the mutation, resulting in the production of a high-quality blastocyst. This suggests that CHK1 dysfunction primarily disrupts crucial biological processes occurring in the cytoplasm. Further investigation reveals that CHK1 mutants have an impact on the F-actin meshwork, leading to disturbances in pronuclear envelope breakdown. Through co-immunoprecipitation and mass spectrometry analysis of around 6000 mouse zygotes, we identified an interaction between CHK1 and MICAL3, a key regulator of F-actin disassembly. The gain-of-function mutants of CHK1 enhance their interaction with MICAL3 and increase MICAL3 enzymatic activity, resulting in excessive depolymerization of F-actin. These findings shed light on the regulatory mechanism behind pronuclear envelope breakdown during the transition from meiosis to the first mitosis in mammals.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4876-4897"},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364831","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

Bacterial RNA sensing by TLR8 requires RNase 6 processing and is inhibited by RNA 2'O-methylation. TLR8 对细菌 RNA 的感应需要 RNase 6 处理，并受到 RNA 2'O- 甲基化的抑制。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-10-03 DOI: 10.1038/s44319-024-00281-9

Ivanéia V Nunes, Luisa Breitenbach, Sarah Pawusch, Tatjana Eigenbrod, Swetha Ananth, Paulina Schad, Oliver T Fackler, Falk Butter, Alexander H Dalpke, Lan-Sun Chen

{"title":"Bacterial RNA sensing by TLR8 requires RNase 6 processing and is inhibited by RNA 2'O-methylation.","authors":"Ivanéia V Nunes, Luisa Breitenbach, Sarah Pawusch, Tatjana Eigenbrod, Swetha Ananth, Paulina Schad, Oliver T Fackler, Falk Butter, Alexander H Dalpke, Lan-Sun Chen","doi":"10.1038/s44319-024-00281-9","DOIUrl":"10.1038/s44319-024-00281-9","url":null,"abstract":"TLR8 senses single-stranded RNA (ssRNA) fragments, processed via cleavage by ribonuclease (RNase) T2 and RNase A family members. Processing by these RNases releases uridines and purine-terminated residues resulting in TLR8 activation. Monocytes show high expression of RNase 6, yet this RNase has not been analyzed for its physiological contribution to the recognition of bacterial RNA by TLR8. Here, we show a role for RNase 6 in TLR8 activation. BLaER1 cells, transdifferentiated into monocyte-like cells, as well as primary monocytes deficient for RNASE6 show a dampened TLR8-dependent response upon stimulation with isolated bacterial RNA (bRNA) and also upon infection with live bacteria. Pretreatment of bacterial RNA with recombinant RNase 6 generates fragments that induce TLR8 stimulation in RNase 6 knockout cells. 2'O-RNA methyl modification, when introduced at the first uridine in the UA dinucleotide, impairs processing by RNase 6 and dampens TLR8 stimulation. In summary, our data show that RNase 6 processes bacterial RNA and generates uridine-terminated breakdown products that activate TLR8.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4674-4692"},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371326","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

Aspartyl proteases target host actin nucleator complex protein to limit epithelial innate immunity. 天冬氨酰蛋白酶以宿主肌动蛋白核聚体蛋白为靶标，限制上皮细胞的先天性免疫。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-09-30 DOI: 10.1038/s44319-024-00270-y

Sandip Patra, Rupinder Kaur

{"title":"Aspartyl proteases target host actin nucleator complex protein to limit epithelial innate immunity.","authors":"Sandip Patra, Rupinder Kaur","doi":"10.1038/s44319-024-00270-y","DOIUrl":"10.1038/s44319-024-00270-y","url":null,"abstract":"Epithelial-immune cell communication is pivotal to control microbial infections. We show that glycosylphosphatidylinositol-linked aspartyl proteases (Yapsins) of the human opportunistic pathogenic yeast Candida glabrata (Cg) thwart epithelial cell (EC)-neutrophil signalling by targeting the EC protein, Arpc1B (actin nucleator Arp2/3 complex subunit), which leads to actin disassembly and impeded IL-8 secretion by ECs. Further, the diminished IL-8 secretion inhibits neutrophil migration, and protects Cg from the neutrophil-mediated killing. CgYapsin-dependent Arpc1B degradation requires Arginine-142 in Arpc1B, and leads to reduced Arpc1B-p38 MAPK interaction and downregulated p38 signalling. Consistently, Arpc1B or p38 deletion promotes survival of the Cg aspartyl protease-deficient mutant in ECs. Importantly, kidneys of the protease-deficient mutant-infected mice display elevated immune cell infiltration and cytokine secretion, implicating CgYapsins in immune response suppression in vivo. Besides delineating Cg-EC interplay, our results uncover a novel target, Arpc1B, that pathogens attack to constrain the host signalling networks, and link Arpc1B mechanistically with p38 activation.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4846-4875"},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343797","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: LncRNA-PAGBC acts as a microRNA sponge and promotes gallbladder tumorigenesis. 作者更正：LncRNA-PAGBC 作为 microRNA 海绵促进胆囊肿瘤发生

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 DOI: 10.1038/s44319-024-00185-8

Xiang-Song Wu, Fang Wang, Huai-Feng Li, Yun-Ping Hu, Lin Jiang, Fei Zhang, Mao-Lan Li, Xu-An Wang, Yun-Peng Jin, Yi-Jian Zhang, Wei Lu, Wen-Guang Wu, Yi-Jun Shu, Hao Weng, Yang Cao, Run-Fa Bao, Hai-Bin Liang, Zheng Wang, Yi-Chi Zhang, Wei Gong, Lei Zheng, Shu-Han Sun, Ying-Bin Liu

引用次数: 0

NS2 induces an influenza A RNA polymerase hexamer and acts as a transcription to replication switch. NS2 可诱导甲型流感 RNA 聚合酶六聚体，并充当转录到复制的开关。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-07-18 DOI: 10.1038/s44319-024-00208-4

Junqing Sun, Lu Kuai, Lei Zhang, Yufeng Xie, Yanfang Zhang, Yan Li, Qi Peng, Yuekun Shao, Qiuxian Yang, Wen-Xia Tian, Junhao Zhu, Jianxun Qi, Yi Shi, Tao Deng, George F Gao

{"title":"NS2 induces an influenza A RNA polymerase hexamer and acts as a transcription to replication switch.","authors":"Junqing Sun, Lu Kuai, Lei Zhang, Yufeng Xie, Yanfang Zhang, Yan Li, Qi Peng, Yuekun Shao, Qiuxian Yang, Wen-Xia Tian, Junhao Zhu, Jianxun Qi, Yi Shi, Tao Deng, George F Gao","doi":"10.1038/s44319-024-00208-4","DOIUrl":"10.1038/s44319-024-00208-4","url":null,"abstract":"Genome transcription and replication of influenza A virus (FluA), catalyzed by viral RNA polymerase (FluAPol), are delicately controlled across the virus life cycle. A switch from transcription to replication occurring at later stage of an infection is critical for progeny virion production and viral non-structural protein NS2 has been implicated in regulating the switch. However, the underlying regulatory mechanisms and the structure of NS2 remained elusive for years. Here, we determine the cryo-EM structure of the FluAPol-NS2 complex at ~3.0 Å resolution. Surprisingly, three domain-swapped NS2 dimers arrange three symmetrical FluPol dimers into a highly ordered barrel-like hexamer. Further structural and functional analyses demonstrate that NS2 binding not only hampers the interaction between FluAPol and the Pol II CTD because of steric conflicts, but also impairs FluAPol transcriptase activity by stalling it in the replicase conformation. Moreover, this is the first visualization of the full-length NS2 structure. Our findings uncover key molecular mechanisms of the FluA transcription-replication switch and have implications for the development of antivirals.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4708-4727"},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723244","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