Biochimie最新文献_第2页

Post-transcriptional modifications and regulation of mRNAs in human mitochondria. 人线粒体mrna转录后修饰和调控

Biochimie Pub Date : 2025-06-25 DOI: 10.1016/j.biochi.2025.06.015

Louise Lambert, Amandine Moretton, Géraldine Farge

{"title":"Post-transcriptional modifications and regulation of mRNAs in human mitochondria.","authors":"Louise Lambert, Amandine Moretton, Géraldine Farge","doi":"10.1016/j.biochi.2025.06.015","DOIUrl":"10.1016/j.biochi.2025.06.015","url":null,"abstract":"Mitochondria contain their own circular genome (mtDNA), which encodes essential components of the oxidative phosphorylation (OXPHOS) system. Mitochondrial DNA transcription is a unique and relatively simple process, requiring a specialized transcription machinery that consists of a RNA polymerase (POLRMT), two transcription factors (TFAM and TFB2M), and an elongation factor (TEFM). During transcription, a non-canonical initiating nucleotide (NCIN) can be incorporated as the first nucleotide, serving as a 5' cap. Mitochondrial transcription produces large polycistronic transcripts, which are subsequently processed by ribonucleases to generate individual messenger RNAs (mt-mRNAs), ribosomal RNAs (mt-rRNAs), and transfer RNAs (mt-tRNAs). This review will specifically focus on the maturation and regulation of mt-mRNAs. Following their release from the primary transcript, mt-mRNAs undergo various post-transcriptional modifications, including methylation, pseudouridylation, and polyadenylation. These modifications play a crucial role in determining mt-mRNAs fate by influencing their stability, translation efficiency, and overall mitochondrial function. Additionally, the spatial organization of these processes within mitochondrial RNA granules (MRGs) suggests a compartmentalized system for mitochondrial gene regulation, ensuring precise coordination between transcription, processing, and translation. A deeper understanding of these post-transcriptional modifications provides valuable insights into mitochondrial gene expression and its broader impact on cellular metabolism.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

5.8S rRNA forms and ribosome heterogeneity in breast cancer. 5.8S rRNA形式与乳腺癌核糖体异质性

Biochimie Pub Date : 2025-05-28 DOI: 10.1016/j.biochi.2025.05.010

Giulia Venturi, Federico Zacchini, Francesca Ruzzi, Angelo Gianluca Corradini, Margherita Serra, Marianna Penzo, Davide Treré, Pier-Luigi Lollini, Lorenzo Montanaro

{"title":"5.8S rRNA forms and ribosome heterogeneity in breast cancer.","authors":"Giulia Venturi, Federico Zacchini, Francesca Ruzzi, Angelo Gianluca Corradini, Margherita Serra, Marianna Penzo, Davide Treré, Pier-Luigi Lollini, Lorenzo Montanaro","doi":"10.1016/j.biochi.2025.05.010","DOIUrl":"10.1016/j.biochi.2025.05.010","url":null,"abstract":"Ribosome heterogeneity can contribute to translation regulation in terms of mRNA selection and translation efficiency. This is particularly true for cancer cells in which oncoribosomes are reported to translate mRNAs encoding for proteins involved in cancer progression. Among other factors, a source of ribosome heterogeneity not yet characterized could be represented by 5.8S rRNA and its three forms distinguished based on their 5' sequence. So far, little is known about the role of the presence of these isoforms in mature ribosomes and how they may contribute to human pathology. Here we investigated the relative abundance of the three 5.8S rRNA isoforms in different contexts. Analyzing total and polysomal RNA from cancer cell lines we detected all the three forms recruited in actively translating ribosomes consistently to the basal levels of their expression. Moreover, we showed that changes in the relative abundance of 5.8S rRNA isoforms can be linked to the process of tumorigenesis in a human HER2 transgenic mouse model which develops spontaneous mammary carcinomas. Finally, from the analysis of breast cancer samples, we observed significant correlations between tumor grade, estrogen receptor status and patient prognosis with the relative abundance of 5.8S rRNA isoforms. These results suggest an additional level of complexity involving 5.8S rRNA and ribosome heterogeneity in cancer pathology.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sterol biosynthesis and phytosterol bioconversion in Crassostrea gigas larvae: new evidence from mass-balance feeding studies. 长牡蛎幼虫的甾醇生物合成和植物甾醇生物转化：来自质量平衡摄食研究的新证据。

Biochimie Pub Date : 2025-05-16 DOI: 10.1016/j.biochi.2025.05.005

Fiz da Costa, Margaux Mathieu-Resuge, Fabienne Le Grand, Claudie Quéré, Gabriel V Markov, Gary H Wikfors, Philippe Soudant

{"title":"Sterol biosynthesis and phytosterol bioconversion in Crassostrea gigas larvae: new evidence from mass-balance feeding studies.","authors":"Fiz da Costa, Margaux Mathieu-Resuge, Fabienne Le Grand, Claudie Quéré, Gabriel V Markov, Gary H Wikfors, Philippe Soudant","doi":"10.1016/j.biochi.2025.05.005","DOIUrl":"10.1016/j.biochi.2025.05.005","url":null,"abstract":"Dietary sterols are important for bivalve larval growth and survival. The aim of the study was to determine quantitatively sterol incorporation and synthesis in Pacific oyster Crassostrea gigas larvae by means of a mass-balance approach. The flow-through larval rearing technique allowed accurate quantification of microalgal ingestion and consequently of sterol ingestion. Sterol incorporation was calculated using the sterol composition of the larvae between 2 sample points. Two sets of experiments were done using two cultured microalgae: Tisochrysis lutea (T) and Chaetoceros neogracile (Cg) as mono- and bi-specific diets (TCg). Accumulation of tissue sterols in oyster larvae, in addition to those present in the diet, indicate that C. gigas larvae appear to have the ability to synthetize sterols de novo under low dietary sterol supply, e.g., when fed the T diet. Sterol synthesis was dependent upon sterol dietary supply; larvae fed T exhibited greater sterol incorporation at the pediveliger stage than larvae fed TCg. Larval sterol compositions under the different dietary regimes indicate likely bioconversion pathways modifying dietary sterols. Larvae fed T bioconverted dietary brassicasterol mainly to cholesterol via a 22-dehydrocholesterol intermediate. Brassicasterol was also actively synthetized in larvae fed T and TCg, suggesting a possible metabolic role of this sterol in C. gigas larvae. Apparent desmosterol synthesis under all experimental conditions suggests a role as a membrane component or as an intermediate in cholesterol synthesis. Our data also indicate that C. gigas larvae require approximately 13 ng cholesterol larvae-1 to achieve competence for metamorphosis. This mass-balance approach will allow the determination of other biochemical requirements in larval nutrition.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The 7SK snRNP complex: a critical regulator in carcinogenesis. 7SK snRNP复合体：癌变的关键调控因子。

Biochimie Pub Date : 2025-05-12 DOI: 10.1016/j.biochi.2025.05.003

Oriana Puidebat, Sylvain Egloff

{"title":"The 7SK snRNP complex: a critical regulator in carcinogenesis.","authors":"Oriana Puidebat, Sylvain Egloff","doi":"10.1016/j.biochi.2025.05.003","DOIUrl":"10.1016/j.biochi.2025.05.003","url":null,"abstract":"Cyclin-Dependent Kinase 9 (CDK9) is a critical regulator of transcriptional elongation, functioning within the Positive Transcription Elongation Factor b (P-TEFb) complex alongside Cyclin T1. P-TEFb facilitates the release of RNA polymerase II (RNAPII) from promoter-proximal pausing, thereby enabling productive transcriptional elongation. CDK9 activity is tightly controlled by the 7SK small nuclear ribonucleoprotein (7SK snRNP) complex, comprising 7SK snRNA, LARP7, MEPCE, and HEXIM1/2. Under homeostatic conditions, the 7SK snRNP sequesters and inactivates a fraction of P-TEFb, maintaining it in a repressed state. However, in response to cellular stress or increased transcriptional demand, P-TEFb is released from 7SK snRNP, activating CDK9 to ensure precise, context-dependent transcriptional control. This regulatory switch allows dynamic adaptation to environmental and intracellular cues. Emerging evidence implicates 7SK snRNP deregulation in cancer progression. This review explores the intricate interplay between 7SK snRNP and CDK9, highlighting how disruptions in individual 7SK snRNP components drive transcriptional imbalances, amplify oncogenic programs, and promote a tumorigenic environment.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The complex post-transcriptional regulation of genes coding for methionine adenosyl transferase: New insights for liver cancer. 蛋氨酸腺苷转移酶基因编码的复杂转录后调控：肝癌的新见解。

Biochimie Pub Date : 2025-05-09 DOI: 10.1016/j.biochi.2025.05.001

Amina Doudou Tellai, Vincent Haghnejad, Justine Antoine, Basma Khemiri Merouani, Jean-Pierre Bronowicki, Natacha Dreumont

{"title":"The complex post-transcriptional regulation of genes coding for methionine adenosyl transferase: New insights for liver cancer.","authors":"Amina Doudou Tellai, Vincent Haghnejad, Justine Antoine, Basma Khemiri Merouani, Jean-Pierre Bronowicki, Natacha Dreumont","doi":"10.1016/j.biochi.2025.05.001","DOIUrl":"10.1016/j.biochi.2025.05.001","url":null,"abstract":"Methionine adenosyltransferases (MATs) catalyze the synthesis of S-adenosylmethionine (SAM), the universal methyl donor involved in methylation reactions, redox balance, and polyamine synthesis. In mammals, three MAT genes, MAT1A, MAT2A, and MAT2B, exhibit tissue-specific expression, with MAT1A predominating in healthy liver and MAT2A/MAT2B upregulated during liver injury and malignancy. A shift from MAT1A to MAT2A/MAT2B expression is a hallmark of hepatocellular carcinoma (HCC), contributing to decreased SAM levels and promoting tumorigenesis. Recent findings highlight the pivotal role of post-transcriptional regulation in controlling MAT gene expression. N6-methyladenosine (m6A) modification, the most prevalent internal mRNA modification, plays a dynamic role in determining the fate of MAT2A mRNA. m6A marks regulate MAT2A mRNA splicing and stability in response to stress and metabolic changes. Additionally, RNA-binding proteins (RBPs) such as ELAVL1 and hnRNPD bind to MAT mRNAs, modulating their stability and translation. Dysregulation of these RBPs in liver disease alters MAT expression profiles. Non-coding RNAs, including microRNAs such as miR-29, miR-21, and miR-485, and long non-coding RNAs such as LINC00662 and SNGH6, modulate MAT expression post-transcriptionally by targeting MAT transcripts directly or influencing RNA-binding proteins (RBPs) and m6A writers/readers. Together, these mechanisms form a complex and intricate post-transcriptional regulatory network that governs MAT activity in physiological and pathological states. This review examines emerging insights into MAT post-transcriptional regulation, focusing on its implications for liver cancer, and opens new avenues for developing therapies that target these regulatory mechanisms.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Master of disguise: ribosomal protein L5 beyond translation. 伪装大师：超越翻译的核糖体蛋白L5。

Biochimie Pub Date : 2025-04-02 DOI: 10.1016/j.biochi.2025.03.009

Guglielmo Rambaldelli, Lorenza Bacci, Daniela Pollutri, Kamil Filipek, Marianna Penzo

{"title":"Master of disguise: ribosomal protein L5 beyond translation.","authors":"Guglielmo Rambaldelli, Lorenza Bacci, Daniela Pollutri, Kamil Filipek, Marianna Penzo","doi":"10.1016/j.biochi.2025.03.009","DOIUrl":"10.1016/j.biochi.2025.03.009","url":null,"abstract":"Ribosomal proteins (RPs), key components of ribosomes, are traditionally associated with protein synthesis. However, emerging evidence suggests their involvement in diverse cellular functions beyond ribosomal biogenesis and translation, including transcriptional regulation. This study aimed at investigating the potential of RPs as transcriptional regulators by analyzing their interacting protein network. A subset of RP interactors exhibiting transcriptional regulatory functions was subjected to Gene Ontology analysis to identify enriched functional pathways. The results indicated that these interactions may play a role in different cellular pathways relevant to a number of biological processes, including cancer. To further explore this hypothesis, a virtual knockdown of RPL5 was performed in ovarian and breast cancer public data. As proof of concept the same experiments were conducted in vitro to validate the computational findings, confirming the potential of RPL5 in transcriptional regulation in cancer. This seminal study provides a foundation for future investigations into the multifaceted roles of RPs in the regulation of gene expression in physiological and pathological contexts.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hijacking a real time detection thermocycler for enzymology: Improvement of a fluorescent bulk assay monitoring helicase activity. 劫持酶学实时检测热循环仪：荧光体检测解旋酶活性的改进。

Biochimie Pub Date : 2025-02-20 DOI: 10.1016/j.biochi.2025.02.002

Jean-Philippe Robin, Vincent Mocquet

引用次数: 0

Highly specific aptamer trap for extremophilic RNA polymerases. 针对嗜极 RNA 聚合酶的高特异性适配体陷阱。

Biochimie Pub Date : 2024-05-15 DOI: 10.1016/j.biochi.2024.05.014

Ivan Petushkov, Andrey Feklistov, Andrey Kulbachinskiy

引用次数: 0

Inside front cover-EDB 内侧前盖EDB

Biochimie Pub Date : 2023-10-17 DOI: 10.1016/S0300-9084(23)00260-2

引用次数: 0

Probing telomeric-like G4 structures with full or partial 2′-deoxy-5-hydroxyuridine substitutions 用2′-脱氧-5-羟基尿苷完全或部分取代探测类端粒G4结构

Biochimie Pub Date : 2023-01-24 DOI: 10.1016/j.biochi.2023.01.009

Zoltán Szeltner , Györgyi Ferenc , Tünde Juhász , Zoltán Kupihár , Zoltán Váradi , Dávid Szüts , Lajos Kovács

{"title":"Probing telomeric-like G4 structures with full or partial 2′-deoxy-5-hydroxyuridine substitutions","authors":"Zoltán Szeltner , Györgyi Ferenc , Tünde Juhász , Zoltán Kupihár , Zoltán Váradi , Dávid Szüts , Lajos Kovács","doi":"10.1016/j.biochi.2023.01.009","DOIUrl":"https://doi.org/10.1016/j.biochi.2023.01.009","url":null,"abstract":"<div>Guanine quadruplexes (G4s) are stable four-stranded secondary DNA structures held together by noncanonical G-G base tetrads. We synthesised the nucleoside analogue 2′-deoxy-5-hydroxyuridine (H) and inserted its phosphoramidite into telomeric repeat-type model oligonucleotides. Full and partial substitutions were made, replacing all guanines in all the three tetrads of a three-tier G4 structure, or only in the putative upper, central, or lower tetrads. We characterised these modified structures using CD, UV absorbance spectroscopy, native gel studies, and a capture oligo-based G4 disruption kinetic assay. The strand separation activity of BLM helicase on these substituted structures was also investigated. Two of the partially H-substituted constructs adopted G4-like structures, but displayed lower thermal stabilities compared to unsubstituted G4. The construct modified in its central tetrad remained mostly denatured, but the possibility of a special structure for the fully replaced variant remained open. H substitutions did not interfere with the G4-resolving activity of BLM helicase, but its efficiency was highly influenced by construct topology and even more by the G4 ligand PhenDC3. Our results suggest that the H modification can be incorporated into G quadruplexes, but only at certain positions to maintain G4 stability. The destabilizing effect observed for 2′-deoxy-5-hydroxyuridine indicates that the cytosine deamination product 5-hydroxyuracil and its nucleoside counterpart in RNA (5-hydroxyuridine), might also be destabilizing in cellular DNA and RNA quadruplexes. The kinetic assay employed in this study can be generally employed for a fast comparison of the stabilities of various G4s either in their free or ligand-bound states.</div>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":"214 ","pages":"Pages 33-44"},"PeriodicalIF":0.0,"publicationDate":"2023-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49670757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0