Molecular and Cellular Biology最新文献_第10页

Investigating the Aggregation and Prionogenic Properties of Human Cancer-Related Proteins. 研究人类癌症相关蛋白的聚集和致朊特性。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-03-31 DOI: 10.1080/10985549.2025.2481054

Dustin Goncharoff, Zhiqiang Du, Shriram Venkatesan, Brandon Cho, Jenny Zhao, Milad J Alasady, Dalton Huey, Hannah Ma, Jake Rosenthal, Alexander Turenitsa, Coral Feldman, Randal Halfmann, Marc L Mendillo, Liming Li

{"title":"Investigating the Aggregation and Prionogenic Properties of Human Cancer-Related Proteins.","authors":"Dustin Goncharoff, Zhiqiang Du, Shriram Venkatesan, Brandon Cho, Jenny Zhao, Milad J Alasady, Dalton Huey, Hannah Ma, Jake Rosenthal, Alexander Turenitsa, Coral Feldman, Randal Halfmann, Marc L Mendillo, Liming Li","doi":"10.1080/10985549.2025.2481054","DOIUrl":"10.1080/10985549.2025.2481054","url":null,"abstract":"Cancer encompasses a range of severe diseases characterized by uncontrolled cell growth and the potential for metastasis. Understanding the mechanism underlying tumorigenesis has been a central focus of cancer research. Self-propagating protein aggregates, known as prions, are linked to various biological functions and diseases, particularly those related to mammalian neurodegeneration. However, it remains unclear whether prion-like mechanisms contribute to tumorigenesis and cancer. Using a combined approach of algorithmic predictions, alongside genetic and biochemical experimentation, we identified numerous cancer-associated proteins prone to aggregation, many of which contain prion-like domains (PrLDs). These predictions were experimentally validated for both aggregation and prion-formation. We demonstrate that several PrLDs undergo nucleation-limited amyloid formation, which can alter protein activity in a mitotically heritable fashion. These include SSXT, a subunit of the chromatin-remodeling BAF (hSWI/SNF) complexes; CLOCK, a core component of the circadian clock; and EPN4, a clathrin-interacting protein involved in protein trafficking between the trans-Golgi network and endosomes. The prions formed by these PrLDs occurred in multiple variants and depended on Hsp104, a molecular chaperone with disaggregase activity. Our results reveal an inherent tendency for prion-like aggregation in human cancer-associated proteins, suggesting a potential role for such aggregation in the epigenetic changes driving tumorigenesis.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"154-168"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Loss of HNRNPK During Cell Senescence Linked to Reduced Production of CDC20. 细胞衰老过程中HNRNPK的丢失与CDC20的产生减少有关。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-01-13 DOI: 10.1080/10985549.2024.2443590

Chang Hoon Shin, Martina Rossi, Krystyna Mazan-Mamczarz, Jennifer L Martindale, Rachel Munk, Apala Pal, Yulan Piao, Jinshui Fan, Supriyo De, Kotb Abdelmohsen, Myriam Gorospe

{"title":"Loss of HNRNPK During Cell Senescence Linked to Reduced Production of CDC20.","authors":"Chang Hoon Shin, Martina Rossi, Krystyna Mazan-Mamczarz, Jennifer L Martindale, Rachel Munk, Apala Pal, Yulan Piao, Jinshui Fan, Supriyo De, Kotb Abdelmohsen, Myriam Gorospe","doi":"10.1080/10985549.2024.2443590","DOIUrl":"10.1080/10985549.2024.2443590","url":null,"abstract":"Cellular senescence is a complex biological response to sublethal damage. The RNA-binding protein HNRNPK was previously found to decrease prominently during senescence in human diploid fibroblasts. Here, analysis of the mechanisms leading to reduced HNRNPK abundance revealed that in cells undergoing senescence, HNRNPK mRNA levels declined transcriptionally and full-length HNRNPK protein was progressively lost, while the abundance of a truncated HNRNPK increased. The ensuing loss of full-length HNRNPK enhanced cell cycle arrest along with increased DNA damage. Analysis of the RNAs enriched after HNRNPK ribonucleoprotein immunoprecipitation (RIP) revealed a prominent target of HNRNPK, CDC20 mRNA, encoding a protein critical for progression through the G2/M phase of the cell division cycle. Silencing HNRNPK markedly decreased the levels of CDC20 mRNA via reduced transcription and stability of CDC20 mRNA, leading to lower CDC20 protein levels; conversely, overexpressing HNRNPK increased CDC20 production. Depletion of either HNRNPK or CDC20 impaired cell proliferation, with a concomitant reduction in the levels of CDK1, a key kinase for progression through G2/M. Given that overexpressing CDC20 in HNRNPK-silenced cells partly alleviated growth arrest, we propose that the reduction in HNRNPK levels in senescent cells contributed to inhibiting proliferation at least in part by suppressing CDC20 production.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"129-141"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971510","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}

引用次数: 0

Noncoding RNA, ncRNA-a3, Epigenetically Regulates TAL1 Transcriptional Program During Erythropoiesis. 非编码RNA， ncRNA-a3，在红细胞生成过程中表观遗传调控TAL1转录程序。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-04-10 DOI: 10.1080/10985549.2025.2482079

Meghana Matur, Yasin Uzun, Xiangguo Shi, Karina Hamamoto, Yi Qiu, Suming Huang

{"title":"Noncoding RNA, ncRNA-a3, Epigenetically Regulates TAL1 Transcriptional Program During Erythropoiesis.","authors":"Meghana Matur, Yasin Uzun, Xiangguo Shi, Karina Hamamoto, Yi Qiu, Suming Huang","doi":"10.1080/10985549.2025.2482079","DOIUrl":"10.1080/10985549.2025.2482079","url":null,"abstract":"Hematopoietic transcription is a combinatorial control of transcription factors, chromatin modifiers, and non-coding RNAs. TAL1 is a critical regulator of normal and malignant hematopoiesis. However, mechanism underlying regulation of TAL1 activity during erythropoiesis versus leukemogenesis remains elusive. Here, we showed that an enhancer RNA, ncRNA-a3 transcribed from TAL1 + 51Kb-enhancer, is positively correlated with TAL1 locus chromatin accessibility and transcription, and required for TAL1 activation during EPO-induced erythropoiesis. Loss of ncRNA-a3 in CD34+ hematopoietic stem and progenitor cells leads to reduction of TAL1 transcription, followed by impaired terminal erythroid differentiation. The effect of ncRNA-a3 loss on erythroid differentiation is partially rescued by overexpression of Tal1 cDNA, suggesting an important role of ncRNA-a3/TAL1 regulatory axis in erythropoiesis. Mechanistically, ncRNA-a3 regulates long-range chromatin interactions between +51Kb erythroid-specific enhancer, promoter and other regulatory elements in the TAL1 locus to maintain the erythroid interaction hub. By facilitating the binding and recruitment of p300/BRG1 to the TAL1 locus, ncRNA-a3 promotes chromatin accessibility in the TAL1 locus and activates TAL1 transcription program, including subsequent epigenetic and transcriptional activation of erythroid-specific TAL1 target genes. Our study reveals a novel role for ncRNA-a3 in TAL1 dependent erythropoiesis and establishes a new mode of ncRNA-a3 action in TAL1 transcriptional activation.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"45 4","pages":"169-184"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Liver Receptor Homolog-1 Deficiency Impairs Alcohol-Associated Liver Disease Owing to Decrease of Aldehyde Dehydrogenase 1 Family Member B1 Gene Expression. 由于醛脱氢酶1家族成员B1基因表达减少，肝脏受体同源物-1缺乏损害酒精相关性肝病

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-05-25 DOI: 10.1080/10985549.2025.2505729

Min-Hee Seo, Jae-Ho Lee, Eun-Ho Lee, Sulagna Mukherjee, Soo-Young Park, Jae-Hoon Bae, Dae-Kyu Song, Seung-Soon Im

{"title":"Liver Receptor Homolog-1 Deficiency Impairs Alcohol-Associated Liver Disease Owing to Decrease of Aldehyde Dehydrogenase 1 Family Member B1 Gene Expression.","authors":"Min-Hee Seo, Jae-Ho Lee, Eun-Ho Lee, Sulagna Mukherjee, Soo-Young Park, Jae-Hoon Bae, Dae-Kyu Song, Seung-Soon Im","doi":"10.1080/10985549.2025.2505729","DOIUrl":"10.1080/10985549.2025.2505729","url":null,"abstract":"Ethanol is detoxified in the liver, and its intake causes hepatic lipid accumulation. The liver receptor homolog-1 (LRH-1) regulates lipid and bile acid metabolism, but its role in ethanol metabolism remains unclear. This study aimed to explore the relationship between ethanol-induced lipid accumulation and LRH-1. To investigate the role of LRH-1 in hepatic ethanol metabolism, LRH-1f/f and liver-specific LRH-1f/cre+ mice were fed a Lieber-DeCarli diet for 3 weeks. The results showed that ethanol-fed LRH-1f/cre+ mice exhibited increased neutral fat, total cholesterol, liver damage markers, and acetaldehyde levels. Moreover, ethanol-fed LRH-1f/cre+ mice displayed decreased fatty acid oxidation, impaired mitochondrial function, and increased reactive oxygen species levels. To identify LRH-1 targets in ethanol metabolism, RNA sequencing analysis revealed significant changes in genes involved in fatty acid metabolism between the control and ethanol groups. Notably, in the absence of LRH-1, ethanol metabolism genes showed a reduction in aldehyde dehydrogenase 1 family member b1 (ALDH1B1) expression. Furthermore, LRH-1 overexpression in HepG2 cells led to increased ALDH1B1 expression, and ChIP sequencing data confirmed the LRH-1 binding peaks in the ALDH1B1 promoter region. In conclusion, this study confirms that LRH-1 depletion results in decreased ALDH1B1 expression, leading to acetaldehyde accumulation and accelerated intrahepatic fat accumulation.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"301-314"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142913","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}

引用次数: 0

Mitogen-Activated Protein Kinase Phosphatase-5 is Required for TGF-β Signaling Through a JNK-Dependent Pathway. 丝裂原活化蛋白激酶磷酸酶-5 是通过 JNK 依赖性途径传递 TGF-β 信号的必要条件

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2024-11-28 DOI: 10.1080/10985549.2024.2426665

Sam Dorry, Sravan Perla, Anton M Bennett

{"title":"Mitogen-Activated Protein Kinase Phosphatase-5 is Required for TGF-β Signaling Through a JNK-Dependent Pathway.","authors":"Sam Dorry, Sravan Perla, Anton M Bennett","doi":"10.1080/10985549.2024.2426665","DOIUrl":"10.1080/10985549.2024.2426665","url":null,"abstract":"Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) constitute members of the dual-specificity family of protein phosphatases that dephosphorylate the MAPKs. MKP-5 dephosphorylates the stress-responsive MAPKs, p38 MAPK and JNK, and has been shown to promote tissue fibrosis. Here, we provide insight into how MKP-5 regulates the transforming growth factor-β (TGF-β) pathway, a well-established driver of fibrosis. We show that MKP-5-deficient fibroblasts in response to TGF-β are impaired in SMAD2 phosphorylation at canonical and non-canonical sites, nuclear translocation, and transcriptional activation of fibrogenic genes. Consistent with this, pharmacological inhibition of MKP-5 is sufficient to block TGF-β signaling, and that this regulation occurs through a JNK-dependent pathway. By utilizing RNA sequencing and transcriptomic analysis, we identify TGF-β signaling activators regulated by MKP-5 in a JNK-dependent manner, providing mechanistic insight into how MKP-5 promotes TGF-β signaling. This study elucidates a novel mechanism whereby MKP-5-mediated JNK inactivation is required for TGF-β signaling and provides insight into the role of MKP-5 in tissue fibrosis.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"17-31"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

miR-365-3p Regulates Gastrointestinal Dysfunction in Diabetes Mellitus Rats via the TLR4/MyD88/NF-κB Pathway. miR-365-3p通过TLR4/MyD88/NF-κB通路调控糖尿病大鼠胃肠道功能障碍

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-07-22 DOI: 10.1080/10985549.2025.2532581

Jiao Xiao, Bin Gao, Yan Xiao, Xiangjie Liu

{"title":"miR-365-3p Regulates Gastrointestinal Dysfunction in Diabetes Mellitus Rats via the TLR4/MyD88/NF-κB Pathway.","authors":"Jiao Xiao, Bin Gao, Yan Xiao, Xiangjie Liu","doi":"10.1080/10985549.2025.2532581","DOIUrl":"10.1080/10985549.2025.2532581","url":null,"abstract":"Over half of diabetes mellitus (DM) patients suffer from gastrointestinal motility disorders. miR-365-3p is involved in DM progression, but its role in gastrointestinal motility disorders remains unclear. This study explored whether miR-365-3p affects gastrointestinal motility in diabetic rats via the TLR4/MyD88/NF-κB pathway. A DM rat model was established using a high-fat, high-sugar diet and injected with a miR-365-3p mimic/inhibitor. DM symptoms, gastric emptying, intestinal propulsion rates, and gastrointestinal transit time were assessed. HE and TUNEL staining evaluated gastrointestinal pathology and apoptosis. qRT-PCR detected miR-365-3p levels, while ELISA assessed gastrointestinal motility-related factors. Immunofluorescence and Western blot analyzed C-kit, TLR4, and pathway proteins. DM rats exhibited increased body weight, blood glucose, and glucose intolerance, with reduced fasting insulin, confirming successful modeling. miR-365-3p was downregulated in DM rats. Injection of miR-365-3p mimic alleviated DM symptoms, reduced gastrointestinal tissue damage and apoptosis, and improved motility. The TLR4 agonist CRX-527 impaired these effects. In conclusion, miR-365-3p overexpression alleviates DM symptoms, gastrointestinal injury, and motility disorders by inhibiting the TLR4/MyD88/NF-κB pathway, offering a potential therapeutic target.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"438-454"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682807","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}

引用次数: 0

The Role of Med15 Sequence Features in Transcription Factor Interactions. Med15序列特征在转录因子相互作用中的作用

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2024-12-24 DOI: 10.1080/10985549.2024.2436672

David G Cooper, Shulin Liu, Emma Grunkemeyer, Jan S Fassler

{"title":"The Role of Med15 Sequence Features in Transcription Factor Interactions.","authors":"David G Cooper, Shulin Liu, Emma Grunkemeyer, Jan S Fassler","doi":"10.1080/10985549.2024.2436672","DOIUrl":"10.1080/10985549.2024.2436672","url":null,"abstract":"Med15 is a general transcriptional regulator and tail module subunit within the RNA Pol II mediator complex. The Saccharomyces cerevisiae Med15 protein has a well-structured N-terminal KIX domain, three activator binding domains (ABDs) and several naturally variable polyglutamine (poly-Q) tracts (Q1, Q2, Q3) embedded in an intrinsically disordered central region, and a C-terminal mediator association domain (MAD). We investigated how the presence of ABDs and changes in length and composition of poly-Q tracts influences Med15 activity using phenotypic, gene expression, transcription factor interaction and phase separation assays of truncation, deletion, and synthetic alleles. We found that individual Med15 activities were influenced by the number of activator binding domains (ABDs) and adjacent polyglutamine tract composition. Robust Med15 activity required at least the Q1 tract and the length of that tract modulated activity in a context-dependent manner. Reduced Msn2-dependent transcriptional activation due to Med15 Q1 tract variation correlated with reduced Msn2:Med15 interaction strength, but interaction strength did not always mirror phase separation propensity. We also observed that distant glutamine tracts and Med15 phosphorylation affected the activities of the KIX domain, and interaction studies revealed that intramolecular interactions may affect some Med15-transcription factor interactions.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"59-78"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882539","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}

引用次数: 0

Small Molecule Screening Identifies HSP90 as a Modifier of RNA Foci in Myotonic Dystrophy Type 1. 小分子筛选发现 HSP90 是肌营养不良症 1 型 RNA 病灶的修饰因子

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2024-10-17 DOI: 10.1080/10985549.2024.2408025

Sara J Johnson, Hannah L Johnson, Reid T Powell, Clifford Stephan, Fabio Stossi, Thomas A Cooper

{"title":"Small Molecule Screening Identifies HSP90 as a Modifier of RNA Foci in Myotonic Dystrophy Type 1.","authors":"Sara J Johnson, Hannah L Johnson, Reid T Powell, Clifford Stephan, Fabio Stossi, Thomas A Cooper","doi":"10.1080/10985549.2024.2408025","DOIUrl":"10.1080/10985549.2024.2408025","url":null,"abstract":"Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by a CTG triplet repeat expansion within the 3' untranslated region of the DMPK gene. Expression of the expanded allele generates RNA containing long tracts of CUG repeats (CUGexp RNA) that form hairpin structures and accumulate in nuclear RNA foci; however, the factors that control DMPK expression and the formation of CUGexp RNA foci remain largely unknown. We performed an unbiased small molecule screen in an immortalized human DM1 skeletal muscle myoblast cell line and identified HSP90 as a modifier of endogenous RNA foci. Small molecule inhibition of HSP90 leads to enhancement of RNA foci and upregulation of DMPK mRNA levels. Knockdown and overexpression of HSP90 in undifferentiated DM1 myoblasts validated the impact of HSP90 with upregulation and downregulation of DMPK mRNA, respectively. Furthermore, we identified p-STAT3 as a downstream mediator of HSP90 impacting levels of DMPK mRNA and RNA foci. Interestingly, differentiated cells exhibited an opposite effect of HSP90 inhibition displaying downregulation of DMPK mRNA through a mechanism independent of p-STAT3 involvement. This study has revealed a novel mediator for DMPK mRNA and foci regulation in DM1 cells with the potential to identify targets for future therapeutic intervention.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"225-237"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

acp³U: A Conserved RNA Modification with Lessons Yet to Unfold. acp³U：一个保守的RNA修饰与教训尚未展开。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-01-06 DOI: 10.1080/10985549.2024.2443138

Mariana D Mandler, Sneha Kulkarni, Pedro J Batista

引用次数: 0

Identification of a Novel Intracellular Function of the Secreted Ribonuclease RNASE1 in Inhibiting Gene Expression. 分泌核糖核酸酶RNASE1在抑制基因表达中的细胞内新功能的鉴定。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-06-17 DOI: 10.1080/10985549.2025.2504972

Ragini Singh, Ahlina Archibald, Xiao Ling Li, Ravi Kumar, Shaoli Das, Erica C Pehrsson, Patrick X Zhao, Xinyu Wen, Raj Chari, Ioannis Grammatikakis, Ashish Lal

{"title":"Identification of a Novel Intracellular Function of the Secreted Ribonuclease RNASE1 in Inhibiting Gene Expression.","authors":"Ragini Singh, Ahlina Archibald, Xiao Ling Li, Ravi Kumar, Shaoli Das, Erica C Pehrsson, Patrick X Zhao, Xinyu Wen, Raj Chari, Ioannis Grammatikakis, Ashish Lal","doi":"10.1080/10985549.2025.2504972","DOIUrl":"10.1080/10985549.2025.2504972","url":null,"abstract":"RNASE1 is a ribonuclease secreted by cells and degrades extracellular RNAs. Here, we unexpectedly found that RNASE1, in addition to being secreted, is predominantly localized to the nucleus and functions to inhibit gene expression in human colorectal cancer (CRC) cells. RNASE1 expression is highly cell type-specific and is restricted to well-differentiated CRC cells where its transcription is activated by the pioneer transcription factor FOXA1. Using CRISPR interference utilizing three independent sgRNAs targeting the RNASE1 locus followed by RNA-seq, we found that upon depletion of RNASE1, most of the differentially expressed RNAs are modestly but significantly upregulated suggesting that RNASE1 predominantly functions to inhibit gene expression. In CRC patients, RNASE1 is significantly downregulated and high RNASE1 expression is associated with better patient survival, indicating a potential tumor suppressive function. Consistent with this, RNASE1 depletion results in increased proliferation and clonogenicity indicating that RNASE1 inhibits the growth of CRC cells. Finally, a promising RNASE1 target among the most significantly upregulated mRNAs upon RNASE1 depletion is DKK1 (Dickkopf inhibitor 1) which is upregulated in CRC and negatively regulated by RNASE1. Collectively, this initial characterization of endogenous RNASE1 uncovers a function of RNASE1 in inhibition of gene expression and CRC cell proliferation.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"315-326"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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