Molecular & Cellular Proteomics最新文献

{"title":"Exploring virus-host interactions through combined proteomic approaches identifies BANF1 as a new essential factor for African Swine Fever Virus.","authors":"Juliette Dupré, Katarzyna Magdalena Dolata, Gang Pei, Aidin Molouki, Lynnette C Goatley, Richard Küchler, Timothy K Soh, Jens B Bosse, Aurore Fablet, Mireille Le Dimna, Grégory Karadjian, Edouard Hirchaud, Christopher L Netherton, Linda K Dixon, Ana Luisa Reis, Damien Vitour, Marie-Frédérique Le Potier, Axel Karger, Grégory Caignard","doi":"10.1016/j.mcpro.2025.101038","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101038","url":null,"abstract":"<p><p>African swine fever virus (ASFV) causes a lethal disease in pigs and represents a significant threat to the global pork industry due to the lack of effective vaccines or treatments. Despite intensive research, many ASFV proteins remain uncharacterized. This study aimed to elucidate the functions of two ASFV proteins, pMGF360-21R and pA151R, through comprehensive analysis of their interactions with host proteins. Using affinity purification-mass spectrometry and yeast two-hybrid screening approaches, we identified the host protein barrier-to-autointegration factor 1 (BANF1) as a key interactor of both viral proteins. Biochemical and colocalization assays confirmed these interactions and demonstrated that MGF360-21R and A151R expression leads to cytoplasmic relocation of BANF1. Functionally, BANF1 silencing significantly reduced ASFV replication, indicating its proviral role. Given BANF1's established function in regulating the cGAS/STING-dependent type I interferon (IFN-I) response, we postulated that A151R and MGF360-21R could inhibit this pathway. Using different strategies, we showed that both A151R and MGF360-21R did indeed inhibit IFN-I induction. Generation of ASFV deficient of A151R or MGF360-21R showed that both mutant viruses enhanced the host IFN response in primary porcine macrophages compared to wild-type virus. However, their capacity to inhibit this pathway could occur through mechanisms independent of BANF1. Proteomic analysis of BANF1 interactors during ASFV infection highlighted potentially roles in chromatin remodeling, nuclear transport, and innate immune response pathways. Altogether, our data provide new insights into ASFV-host interactions, identifying BANF1 as an important new host factor required for replication and uncovering novel functions for A151R and MGF360-21R.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101038"},"PeriodicalIF":6.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accurate MS-based diagnostic amyloid typing using endogenously normalized protein intensities in formalin-fixed paraffin-embedded tissue.","authors":"Vanessa Hollfoth, Arslan Ali, Eyyub Bag, Philip Riemenschneider, Sven Mattern, Julia Luibrand, Mohamed Ali Jarboui, Kerstin Singer, Benjamin Goeppert, Mirita Franz-Wachtel, Martina Sauter, Shabnam Asadikomeleh, Tobias Feilen, Christian Hentschker, Silvia Ribback, Elke Hammer, Karsten Boldt, Frank Dombrowski, Oliver Schilling, Boris Macek, Marius Ueffing, Karin Klingel, Stephan Singer","doi":"10.1016/j.mcpro.2025.101040","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101040","url":null,"abstract":"<p><p>Amyloidoses are a group of diseases characterized by the pathological deposition of non-degradable misfolded protein fibrils, including those associated with plasma cell neoplasias, chronic inflammatory conditions, and age-related disorders, among others. Precise identification of the fibril-forming and thereby amyloidosis type defining protein is crucial for prognosis and correct therapeutic intervention. While immunohistochemistry (IHC) is widely used for amyloid typing, it requires extensive interpretation expertise and can be limited by inconclusive staining results. Thus, mass spectrometry (MS), if available, has been proposed as the preferred method for amyloid typing by international specialized centers (USA, UK) using primarily spectral counts for quantification. Here, we introduce an alternative method of relative quantification to further enhance the accuracy and reliability of proteomic amyloid typing. We analyzed 62 formalin-fixed, paraffin-embedded (FFPE) tissue samples, primarily endomyocardial biopsies, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and employed internal normalization of iBAQ values of amyloid-related proteins relative to serum amyloid P component (APCS) for amyloidosis typing. The APCS method demonstrated robust performance across multiple LC-MS/MS platforms and achieved complete concordance with clear cut IHC typed amyloidosis cases. More importantly, it resolved unclear amyloid cases with inconclusive staining results. Additionally, for samples without a distinct fibril-forming protein identified in the standard procedure, de novo sequencing uncovered immunoglobulin light chain components, enabling the diagnosis of rare AL-amyloidosis subtypes. Finally, we established machine learning approach (XGBoost) achieving 94% accuracy by using ∼160 amyloid-related proteins as input variables. In summary, the iBAQ APCS normalization method extended by de novo sequencing allows robust, accurate, and reliable diagnostic amyloid typing, and can be complemented by an AI-based classification. Careful reviewing of each histological sample and the clinical context, nevertheless, remains indispensable for accurate interpretation.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101040"},"PeriodicalIF":6.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An automated workflow to address proteome complexity and the large search space problem in proteomics and HLA-I immunopeptidomics.","authors":"Yehor Horokhovskyi, Hanna P Roetschke, John A Cormican, Martin Pašen, Sina Garazhian, Michele Mishto, Juliane Liepe","doi":"10.1016/j.mcpro.2025.101039","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101039","url":null,"abstract":"<p><p>Antigenic noncanonical epitope and novel protein discovery are research areas with therapeutical applications, predominantly done via mass spectrometry. The latter should rely on a well-characterized proteogenomic search space. Its size is barely known for antigenic noncanonical peptides and novel proteins, and this could impact on their identification. To address these issues, we here develop an automated workflow comprised of Sequoia for the creation of RNA sequencing informed and exhaustive sequence search spaces for various noncanonical peptide origins, and SPIsnake for pre-filtering and exploration of sequence search space prior to mass spectrometry searches. We apply our workflow to characterize the exact sizes of tryptic and nonspecific peptide sequence search spaces in a variety of definitions, their reduction when using RNA expression, their inflation by post-translational modifications, and the frequency of peptide sequence multimapping to different noncanonical origins. Furthermore, we explore the application of Sequoia and SPIsnake on HLA-I immunopeptidomes, thereby rescuing sensitivity in peptide identification when confronted with inflated search spaces. Taken together, Sequoia and SPIsnake pave the way for an educated development of methods addressing large-scale exhaustive proteogenomic discovery by exposing the consequences of database size inflation and ambiguity of peptide and protein sequence identification.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101039"},"PeriodicalIF":6.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial proteomics reveals distinct protein patterns in cortical migration disorders caused by LIN28A overexpression and WNT activation.","authors":"Jelena Navolić, Sara Hawass, Manuela Moritz, Jan Hahn, Maximilian Middelkamp, Antonia Gocke, Matthias Dottermusch, Yannis Schumann, Lisa Ruck, Christoph Krisp, Shweta Godbole, Piotr Sumislawski, Nele Köppen, Elisabetta Gargioni, Hartmut Schlüter, Julia E Neumann","doi":"10.1016/j.mcpro.2025.101037","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101037","url":null,"abstract":"<p><p>Developmental signalling pathways act in stage and tissue dependent relation and mis-activation can drive tumour formation. The RNA-binding protein LIN28A binds to mRNA and miRNA and thereby affects the protein turnover and maintains stemness. LIN28A is overexpressed in embryonal brain tumours which show low correlation between transcriptome and proteome signatures. Additionally, stabilising CTNNB1 mutations activating the WNT pathway have been reported in brain tumours with LIN28A overexpression. The aim of this study was to co-activate these oncogenic proteins during embryonal brain development and investigate the histomorphology of the cerebral cortex in relation to proteome levels with spatial resolution using the nanosecond infrared laser (NIRL) system for nano-volume sampling. The combination of both oncogenic factors in in vivo model did not lead to brain tumour formation during embryonal development but resulted in disturbed lamination and impaired cell migration in the cerebral cortex. Spatially resolved proteome analysis of the cortices reveal unique layer signatures across ablated layers. Moreover, the extracellular matrix receptors RPSA and ITGB1 were spatially disturbed comparing the mouse models and accompanied by a porous pial border and overmigration of neural cells. Cajal-Retzius cells were misplaced in deeper cortex regions without affecting general REELIN levels. Additionally, the glycosylated levels of α-DYSTROGLYCAN were reduced in this model. Taken together, the interplay of LIN28A and CTNNB1 resulted in a cortical migration disorder showing histomorphological and molecular similarities to human Cobblestone lissencephaly (type 2) disorder. This highlights novel implications of the oncogene LIN28A in extracellular matrix integrity.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101037"},"PeriodicalIF":6.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Professor D.F. Hunt relationship with Finnigan Corporation and His Impact on Mass Spectrometer Development.","authors":"Michael S Story, George C Stafford, John E P Syka","doi":"10.1016/j.mcpro.2025.101033","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101033","url":null,"abstract":"<p><p>Don Hunt's 50-year collaboration with Finnigan Instruments Corporation has resulted in many innovations in mass spectrometry that range from new instrumentation to new analytical methodologies which in turn enabled new applications. The fruits of this collaboration, directly and indirectly, have had a broad and enduring impact on the instrumentation and practice of modern mass spectrometry. The authors of this monograph were members of the research and development team at Finnigan over time frames that collectively encompass the entirety of the collaboration. This article provides a narrative history and chronology of the Hunt-Finnigan relationship based on their personal recollections as well as the recollections of other participants.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101033"},"PeriodicalIF":6.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mTORC2 regulates non-homologous end joining through modulating the temporal dynamics of 53BP1.","authors":"Chunqing Wang, Hao Wang, Yunqiu Wang, Mingming Xiao, Xiaoxuan Song, Xiaofei Wang, Xiaofang Zhang, Kexing Jin, Dongqing Zhao, Hanxiang Chen, Ning Zhang, Ruibing Chen","doi":"10.1016/j.mcpro.2025.101035","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101035","url":null,"abstract":"<p><p>DNA damage repair is a critical biological process that maintains genomic integrity, and its dysregulation is closely related to tumorigenesis. To reveal the roles of mammalian target of rapamycin complex 2 (mTORC2) in DNA damage response (DDR), we investigated the temporal changes of cellular protein phosphorylation in mTORC2 deficient renal cancer cells in response to DNA double-strand break (DSB) induced by ionizing radiation (IR) using quantitative phosphoproteomics. The results showed that knockdown of Rictor, a specific component of mTORC2, induced profound changes in the dynamics of protein phosphorylation in response to IR. Intriguingly, the phosphorylation levels of multiple signaling molecules from the non-homologous end joining (NHEJ) pathway were affected by Rictor. Mechanistic study revealed that mTORC2 could regulate the spatiotemporal dynamics of p53 binding protein 1 (53BP1) in DDR. Rictor knockdown changed the phosphorylation of 53BP1 at multiple Ser/Thr sites. The efficiency of NHEJ was significantly reduced in Rictor deficient cells, and the maintenance of 53BP1 nuclear foci induced by IR was prolonged. Furthermore, mTORC2 modulated DSB repair through protein kinase B (PKB/Akt) and cyclin-dependent kinase 1 (CDK1). Finally, Rictor knockdown conferred hypersensitivity to IR and chemotherapeutic treatment in renal cancer cells, implying the potential use of the combination of mTORC2 inhibition with genotoxic therapy for renal cancer treatment.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101035"},"PeriodicalIF":6.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics characterization of acquired Olaparib resistance in BRCA1 and BRCA2 mutant breast cancer cell lines.","authors":"Holda A Anagho-Mattanovich, Meeli Mullari, Matthias Anagho-Mattanovich, Hayoung Cho, Anna-Kathrine Pedersen, Oana Palasca, Jesper V Olsen, Marie Locard-Paulet, Michael L Nielsen","doi":"10.1016/j.mcpro.2025.101034","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101034","url":null,"abstract":"<p><p>Poly (ADP-ribose) polymerase inhibitors (PARPi) are widely used as targeted therapies against breast cancers with BRCA mutations. However, the development of resistance to PARPi poses a significant challenge for long-term efficacy of these therapies, warranting further understanding of mechanisms of PARPi resistance. Here, we generated and characterized Olaparib resistance (OR) in BRCA1/2 mutant breast cancer cell lines MDAMB436 and HCC1428 using a systems-level multi-omics approach, including transcriptome, proteome, phosphoproteome, and ADP-ribosylation analysis. Our analyses revealed that resistance development strongly correlated with protein expression changes, while modest effects on phosphorylation- and ADP-ribosylation-dependent signaling pathways were observed. We found that BRCA1 expression was reestablished in OR MDAMB436 cell lines, while PARP1 expression was decreased. In OR HCC1428 cell lines, the BRCA2 mutation was not reverted. However, we observed increased expression of Fanconi anemia group D2 (FANCD2), histone parylation factor 1 (HPF1), and Nicotinamide phosphoribosyltransferase (NAMPT) in various cell lines, suggesting increased replication fork protection, and changes in the ADPr pathway and adaptation of metabolic pathways as resistance mechanisms. Our findings provide valuable insights into the complex landscape of PARPi resistance, offering potential targets for further investigation and therapeutic intervention.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101034"},"PeriodicalIF":6.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting Branch-Specific Unfolded Protein Response Activation in Drug-Tolerant BRAF-Mutant Melanoma using Data-Independent Acquisition Mass Spectrometry.","authors":"Lea A Barny, Jake N Hermanson, Sarah K Garcia, Philip E Stauffer, Lars Plate","doi":"10.1016/j.mcpro.2025.101036","DOIUrl":"10.1016/j.mcpro.2025.101036","url":null,"abstract":"<p><p>Cells rely on the Unfolded Protein Response (UPR) to maintain ER protein homeostasis (proteostasis) when faced with elevated levels of misfolded and aggregated proteins. The UPR is comprised of three main branches-ATF6, IRE1, and PERK-that coordinate the synthesis of proteins involved in folding, trafficking, and degradation of nascent proteins to restore ER function. Dysregulation of the UPR is linked to numerous diseases, including neurodegenerative disorders, cancer, and diabetes. Despite its importance, identifying UPR targets has been challenging due to their heterogeneous induction, which varies by cell type and tissue. Additionally, defining the magnitude and range of UPR-regulated genes is difficult because of intricate temporal regulation, feedback between UPR branches, and extensive cross-talk with other stress-signaling pathways. To comprehensively identify UPR-regulated proteins and determine their branch specificity, we developed a data-independent acquisition (DIA) liquid-chromatography mass spectrometry (LC-MS) pipeline. Our optimized workflow improved identifications of low-abundant UPR proteins and leveraged an automated SP3-based protocol on the Biomek i5 liquid handler for label-free peptide preparation. Using engineered stable cell lines that enable selective pharmacological activation of each UPR branch without triggering global UPR activation, we identified branch-specific UPR proteomic targets. These targets were subsequently applied to investigate proteomic changes in multiple BRAF-mutant melanoma cell lines treated with a BRAF inhibitor (PLX4720, i.e., vemurafenib). Our findings revealed differential regulation of the XBP1s branch of the UPR in the BRAF-mutant melanoma cell lines after PLX4720 treatment, likely due to calcium activation, suggesting that the UPR plays a role as a non-genetic mechanism of drug tolerance in melanoma. In conclusion, the validated branch-specific UPR proteomic targets identified in this study provide a robust framework for investigating this pathway across different cell types, drug treatments, and disease conditions in a high-throughput manner.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101036"},"PeriodicalIF":6.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secretagogin Downregulation Impairs Nerve Cell Migration in Hirschsprung Disease via Inhibition of the LEF-1/NCAM1 Axis.","authors":"Yun Zhou, Shuiqing Chi, Shuai Li, Zhibin Luo, Liying Rong, Mengxin Zhang, Yunshang Chen, Jialing Guo, Dehua Yang, Xi Zhang, Guoqing Cao, Shao-Tao Tang","doi":"10.1016/j.mcpro.2025.101032","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101032","url":null,"abstract":"<p><p>Hirschsprung disease (HSCR) is a common peripheral neurodevelopmental disorder, and impaired enteric neural crest cell (ENCC) migration is one of the key factors. Secretagogin (SCGN) has been demonstrated to play a critical role in the rostral migratory stream during central nerve regeneration. However, there is a paucity of knowledge on the role of SCGN in ENCC migration. Here we revealed a significant downregulation of SCGN by protein profiles using tandem mass tag (TMT) in HSCR lesion colon tissues. We identified decreased expression of SCGN could hinder cell migration in vitro and in vivo. Mechanistically, SCGN upregulated the transcription factor LEF-1, which directly activated the transcription of the cell adhesion molecule NCAM1, thereby promoting cell migration. In conclusion, this study elucidates the role of SCGN in HSCR pathogenesis by demonstrating its involvement in affecting neural crest cell migration through the LEF-1/NCAM1 axis. The findings could contribute to the diagnostic and therapeutic strategies for HSCR.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101032"},"PeriodicalIF":6.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleolar proteomics revealed the regulation of RNA exosome localization by MTR4.","authors":"Yaqian Zhang, Guangzhen Jiang, Ke Wang, Minjie Hong, Xinya Huang, Xiangyang Chen, Xuezhu Feng, Shouhong Guang","doi":"10.1016/j.mcpro.2025.101031","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101031","url":null,"abstract":"<p><p>The nucleolus is the largest membrane-less organelle within the nucleus and plays critical roles in regulating the cell cycle, senescence, and stress responses. The RNA exosome is a multiprotein ribonucleolytic complex involved in RNA processing and degradation in the cytoplasm, the nucleus, and the nucleolus. Previous studies have shown that the subcellular localization of the RNA exosome is crucial for its function. However, the mechanism that regulates its spatial distribution remains largely unexplored. In this study, we identified the nuclear RNA helicase MTR4 as a regulator of the RNA exosome localization through nucleolar quantitative proteomics technology. Immunostaining and fluorescence tagging confirmed that the depletion of MTR4 resulted in the translocation of the RNA exosome subunits from the nucleolus to the nucleoplasm. Notably, the translocation is specifically regulated by MTR4 and does not depend on other cofactors of the MTR4-containing TRAMP, PAXT, and NEXT complexes. The nucleolar accumulation of exosome subunits mutually depends on other exosome subunits. Additionally, actinomycin D treatment, which inhibits transcription, induced the RNA exosome to translocate from the nucleolus to the nucleoplasm, likely through the regulation of nucleolar MTR4 levels. These findings uncover a regulatory mechanism that modulates the localization of the RNA exosome within the nucleolus.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101031"},"PeriodicalIF":6.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}