Nature Cell Biology最新文献_第6页

Functional screen identifies RBM42 as a mediator of oncogenic mRNA translation specificity

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-02-04 DOI: 10.1038/s41556-024-01604-7

Joanna R. Kovalski, Goksu Sarioglu, Vishvak Subramanyam, Grace Hernandez, Gilles Rademaker, Juan A. Oses-Prieto, Macey Slota, Nimmy Mohan, Kaylee Yiakis, Isabelle Liu, Kwun Wah Wen, Grace E. Kim, Sohit Miglani, Alma L. Burlingame, Hani Goodarzi, Rushika M. Perera, Davide Ruggero

{"title":"Functional screen identifies RBM42 as a mediator of oncogenic mRNA translation specificity","authors":"Joanna R. Kovalski, Goksu Sarioglu, Vishvak Subramanyam, Grace Hernandez, Gilles Rademaker, Juan A. Oses-Prieto, Macey Slota, Nimmy Mohan, Kaylee Yiakis, Isabelle Liu, Kwun Wah Wen, Grace E. Kim, Sohit Miglani, Alma L. Burlingame, Hani Goodarzi, Rushika M. Perera, Davide Ruggero","doi":"10.1038/s41556-024-01604-7","DOIUrl":"10.1038/s41556-024-01604-7","url":null,"abstract":"Oncogenic protein dosage is tightly regulated to enable cancer formation but how this is regulated by translational control remains unknown. The Myc oncogene is a paradigm of an exquisitely regulated oncogene and a driver of pancreatic ductal adenocarcinoma (PDAC). Here we use a CRISPR interference screen in PDAC cells to identify activators of selective MYC translation. The top hit, the RNA-binding protein RBM42, is highly expressed in PDAC and predicts poor survival. We show that RBM42 binds and selectively regulates the translation of MYC and a precise suite of pro-oncogenic transcripts, including JUN and EGFR. Mechanistically, we find that RBM42 binds and remodels the MYC 5′ untranslated region structure, facilitating the formation of the translation pre-initiation complex. Importantly, RBM42 is necessary for PDAC tumorigenesis in a Myc-dependent manner in vivo. This work transforms the understanding of the translational code in cancer and illuminates therapeutic openings to target the expression of oncogenes. Kovalski et al. perform a genome-wide CRISPRi screen for selective MYC mRNA translation regulators and identify RBM42 as a ribosome-associated protein that modulates translation of MYC and an oncogenic mRNA programme required for pancreatic cancer growth.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 3","pages":"518-529"},"PeriodicalIF":17.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083421","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

How a ribosomal protein avoids mixed signals

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-31 DOI: 10.1038/s41556-024-01606-5

Kanda M. Borgognoni, Robin E. Stanley

引用次数: 0

Cytoplasmic flow is a cell size sensor that scales anaphase

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-31 DOI: 10.1038/s41556-024-01605-6

Olga Afonso, Ludovic Dumoulin, Karsten Kruse, Marcos Gonzalez-Gaitan

{"title":"Cytoplasmic flow is a cell size sensor that scales anaphase","authors":"Olga Afonso, Ludovic Dumoulin, Karsten Kruse, Marcos Gonzalez-Gaitan","doi":"10.1038/s41556-024-01605-6","DOIUrl":"10.1038/s41556-024-01605-6","url":null,"abstract":"During early embryogenesis, fast mitotic cycles without interphase lead to a decrease in cell size, while scaling mechanisms must keep cellular structures proportional to cell size. For instance, as cells become smaller, if the position of nuclear envelope reformation (NER) did not adapt, NER would have to occur beyond the cell boundary. Here we found that NER position in anaphase scales with cell size via changes in chromosome motility, mediated by cytoplasmic flows that themselves scale with cell size. Flows are a consequence of friction between viscous cytoplasm and bulky cargo transported by dynein on astral microtubules. As an emerging property, confinement in cells of different sizes yields scaling of cytoplasmic flows. Thus, flows behave like a cell geometry sensor: astral microtubules approach the boundary causing flow velocity changes, which then affect the velocity of chromosome separation, thus scaling NER. Afonso et al. show that, during anaphase, chromosome movement can be driven by large cytoplasmic flows. These dynein-dependent cytoplasmic flows scale with cell size, slowing in smaller cells, thereby scaling anaphase.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 2","pages":"273-282"},"PeriodicalIF":17.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01605-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071944","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

SNORD113–114 cluster maintains haematopoietic stem cell self-renewal via orchestrating the translation machinery

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-31 DOI: 10.1038/s41556-024-01593-7

Hui Wang, Zhaoru Zhang, Chenxi Han, Penglei Jiang, Jiayue Xu, Yingli Han, Deyu Huang, Jian Li, Jie Zhou, Michael Durnin, Shiyuan Chen, Yaxin Liu, Jinghao Sheng, Jie Cao, Jianzhao Liu, Bing Liu, Jia Yu, Fang Wang, Pengxu Qian

{"title":"SNORD113–114 cluster maintains haematopoietic stem cell self-renewal via orchestrating the translation machinery","authors":"Hui Wang, Zhaoru Zhang, Chenxi Han, Penglei Jiang, Jiayue Xu, Yingli Han, Deyu Huang, Jian Li, Jie Zhou, Michael Durnin, Shiyuan Chen, Yaxin Liu, Jinghao Sheng, Jie Cao, Jianzhao Liu, Bing Liu, Jia Yu, Fang Wang, Pengxu Qian","doi":"10.1038/s41556-024-01593-7","DOIUrl":"10.1038/s41556-024-01593-7","url":null,"abstract":"Haematopoietic stem cells (HSCs) self-renew and differentiate to replenish the pool of blood cells, which require a low but finely tuned protein synthesis rate. Nonetheless, the translatome landscape in HSCs and how the translation machinery orchestrates HSC self-renewal remain largely elusive. Here we perform ultra-low-input Ribo-seq in HSCs, progenitor and lineage cells, and reveal HSC-specific translated genes involved in rRNA processing. We systematically profile small nucleolar RNAs (snoRNAs) and uncover an indispensable role of the SNORD113–114 cluster in regulating HSC self-renewal. Maternal knockout (Mat-KO) of this cluster substantially impairs HSC self-renewal, whereas loss of the paternal allele shows no obvious phenotype. Mechanistically, Mat-KO results in dysregulation of translation machinery (rRNA 2′-O-Me modifications, pre-rRNA processing, 60S ribosome assembly and translation) and induces nucleolar stress in HSCs, which exempts p53 from Mdm2-mediated proteasomal degradation and leads to apoptosis. Collectively, our study provides a promising facet to our understanding of snoRNA-mediated regulation in HSC homeostasis. Wang et al. profile the translatome of haematopoietic stem cells (HSCs) and downstream progenitors and lineages. They identify the SNORD113–114 cluster as a modulator of translation and self-renewal in HSCs.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 2","pages":"246-261"},"PeriodicalIF":17.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071943","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

Flow, sense and divide

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-31 DOI: 10.1038/s41556-024-01591-9

Nicoletta I. Petridou

引用次数: 0

An avoidance segment resolves a lethal nuclear–mitochondrial targeting conflict during ribosome assembly

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-31 DOI: 10.1038/s41556-024-01588-4

Michaela Oborská-Oplová, Alexander Gregor Geiger, Erich Michel, Purnima Klingauf-Nerurkar, Sven Dennerlein, Yury S. Bykov, Simona Amodeo, André Schneider, Maya Schuldiner, Peter Rehling, Vikram Govind Panse

{"title":"An avoidance segment resolves a lethal nuclear–mitochondrial targeting conflict during ribosome assembly","authors":"Michaela Oborská-Oplová, Alexander Gregor Geiger, Erich Michel, Purnima Klingauf-Nerurkar, Sven Dennerlein, Yury S. Bykov, Simona Amodeo, André Schneider, Maya Schuldiner, Peter Rehling, Vikram Govind Panse","doi":"10.1038/s41556-024-01588-4","DOIUrl":"10.1038/s41556-024-01588-4","url":null,"abstract":"The correct sorting of nascent ribosomal proteins from the cytoplasm to the nucleus or to mitochondria for ribosome production poses a logistical challenge for cellular targeting pathways. Here we report the discovery of a conserved mitochondrial avoidance segment (MAS) within the cytosolic ribosomal protein uS5 that resolves an evolutionary lethal conflict between the nuclear and mitochondrial targeting machinery. MAS removal mistargets uS5 to the mitochondrial matrix and disrupts the assembly of the cytosolic ribosome. The resulting lethality can be rescued by impairing mitochondrial import. We show that MAS triages nuclear targeting by disabling a cryptic mitochondrial targeting activity within uS5 and thereby prevents fatal capture by mitochondria. Our findings identify MAS as an essential acquisition by the primordial eukaryote that reinforced organelle targeting fidelity while developing an endosymbiotic relationship with its mitochondrial progenitor. Oborská-Oplová et al. report a conserved mitochondrial avoidance segment in the cytosolic ribosomal protein uS5 that prevents mistargeting of uS5 to the mitochondrial matrix and ensures cytosolic ribosomal assembly.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 2","pages":"336-346"},"PeriodicalIF":17.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071939","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

Multiomics reveals that triacylglycerol mobilization helps drive recovery from mitochondrial stress

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-24 DOI: 10.1038/s41556-024-01603-8

引用次数: 0

Mitochondrial protein import stress 线粒体蛋白输入应激

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-22 DOI: 10.1038/s41556-024-01590-w

Nikolaus Pfanner, Fabian den Brave, Thomas Becker

{"title":"Mitochondrial protein import stress","authors":"Nikolaus Pfanner, Fabian den Brave, Thomas Becker","doi":"10.1038/s41556-024-01590-w","DOIUrl":"10.1038/s41556-024-01590-w","url":null,"abstract":"Mitochondria have to import a large number of precursor proteins from the cytosol. Chaperones keep these proteins in a largely unfolded state and guide them to the mitochondrial import sites. Premature folding, mitochondrial stress and import defects can cause clogging of import sites and accumulation of non-imported precursors, representing a critical burden for cellular proteostasis. Here we discuss how cells respond to mitochondrial protein import stress by regenerating clogged import sites and inducing stress responses. The mitochondrial protein import machinery has a dual role by serving as sensor for detecting mitochondrial dysfunction and inducing stress-response pathways. The production of chaperones that fold or sequester precursor proteins in deposits is induced and the proteasomal activity is increased to remove the excess precursor proteins. Together, these pathways reveal how mitochondria are tightly integrated into a cellular proteostasis and stress response network to maintain cell viability. Cells respond to mitochondrial protein import stress by regenerating clogged import sites and inducing stress responses. Mitochondria are thus tightly integrated into the cellular proteostasis and stress-response network to maintain cell viability.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 2","pages":"188-201"},"PeriodicalIF":17.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991965","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

Battling Diamond-Blackfan anaemia 与钻石型黑斑贫血症作斗争

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-16 DOI: 10.1038/s41556-024-01599-1

Stylianos Lefkopoulos

引用次数: 0

Tripotency in human pancreas 人体胰腺的三效性

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-16 DOI: 10.1038/s41556-024-01601-w

Stylianos Lefkopoulos

引用次数: 0