☆ 4.8 Article

HIF-driven SF3B1 induces KHK-C to enforce fructolysis and heart disease

NATURE (2015)

获取全文
添加到收藏夹

期刊

NATURE
卷 522, 期 7557, 页码 444-+

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/nature14508

关键词

-

类别

Multidisciplinary Sciences

资金

  1. Sinergia (Swiss National Science Foundation)
  2. Swiss Heart Foundation
  3. MRC [MC_U105185859, MC_U105185858] Funding Source: UKRI
  4. Medical Research Council [MC_U105185858, MC_U105185859] Funding Source: researchfish

向作者/读者索取更多资源

Protocol

社区支持

Reagent

社区支持

Fructose is a major component of dietary sugar and its overconsumption exacerbates key pathological features of metabolic syndrome. The central fructose-metabolising enzyme is ketohexokinase (KHK), which exists in two isoforms: KHK-A and KHK-C, generated through mutually exclusive alternative splicing of KHK pre-mRNAs. KHK-C displays superior affinity for fructose compared with KHK-A and is produced primarily in the liver, thus restricting fructose metabolism almost exclusively to this organ. Here we show that myocardial hypoxia actuates fructose metabolism in human and mouse models of pathological cardiac hypertrophy through hypoxia-inducible factor 1 alpha (HIF1 alpha) activation of SF3B1 and SF3B1-mediated splice switching of KHK-A to KHK-C. Heart-specific depletion of SF3B1 orgenetic ablation of Khk, but not Khk-A alone, in mice, suppresses pathological stress-induced fructose metabolism, growth and contractile dysfunction, thus defining signalling components and molecular underpinnings of a fructose metabolism regulatory system crucial for pathological growth.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Clinical Neurology

RNA polymerase II-associated proteins reveal pathways affected in VCP-related amyotrophic lateral sclerosis

Mahmoud-Reza Rafiee, Sara Rohban, Karen Davey, Jernej Ule, Nicholas M. Luscombe

Summary: Valosin-containing protein (VCP) is a hexameric ATPase associated with cellular activities and its mutations are linked to neurodegenerative diseases. The study reveals that VCP mutations impair the binding of transcriptional machinery and mRNA splicing proteins to RNA polymerase II (RNAPII), leading to aberrant alternative splicing and proteinopathy in neurodegeneration.

BRAIN (2023)

添加到收藏夹
Article Oncology

ROS Induction Targets Persister Cancer Cells with Low Metabolic Activity in NRAS-Mutated Melanoma

Ossia M. Eichhoff, Corinne I. Stoffel, Jan Kasler, Luzia Briker, Patrick Turko, Gergely Karsai, Nina Zila, Verena Paulitschke, Phil F. Cheng, Alexander Leitner, Andrea Bileck, Nicola Zamboni, Anja Irmisch, Zsolt Balazs, Aizhan Tastanova, Susana Pascoal, Pal Johansen, Rebekka Wegmann, Julien Mena, Alaa Othman, Vasanthi S. Viswanathan, Judith Wenzina, Andrea Aloia, Annalisa Saltari, Andreas Dzung, Michael Krauthammer, Stuart L. Schreiber, Thorsten Hornemann, Martin Distel, Berend Snijder, Reinhard Dummer, Mitchell P. Levesque

Summary: The clinical management of NRAS-mutated melanomas is challenging due to resistance that arises through genetic, transcriptional, and metabolic adaptation. However, the adoption of a mesenchymal phenotype with a quiescent metabolic program in NRAS-mutated melanoma cells confers sensitivity to reactive oxygen species (ROS) induction, which can be inhibited by ROS inducers in combination with MAPK pathway inhibitors. The findings suggest that targeting both metabolic reprogramming and MAPK signaling could improve patient treatment in melanoma and other cancers.

CANCER RESEARCH (2023)

添加到收藏夹
Review Biochemistry & Molecular Biology

Recent advances in mass spectrometry-based computational metabolomics

Timothy M. D. Ebbels, Justin J. J. van der Hooft, Haley Chatelaine, Corey Broeckling, Nicola Zamboni, Soha Hassoun, Ewy A. Mathe

Summary: The computational metabolomics field brings together experts from various disciplines to maximize the impact of metabolomics research. Advances in technology have generated complex datasets that require processing, annotation, modeling, and interpretation. Techniques for visualization, integration, and interpretation of metabolomics data have evolved alongside the development of databases and knowledge resources. This review highlights recent advances and discusses opportunities and innovations in response to challenges in the field.

CURRENT OPINION IN CHEMICAL BIOLOGY (2023)

添加到收藏夹
Article Biochemistry & Molecular Biology

HNRNPH1 regulates the neuroprotective cold-shock protein RBM3 expression through poison exon exclusion

Julie Qiaojin Lin, Deepak Khuperkar, Sofia Pavlou, Stanislaw Makarchuk, Nikolaos Patikas, Flora C. Y. Lee, Julia M. Zbiegly, Jianning Kang, Sarah F. Field, David M. D. Bailey, Joshua L. Freeman, Jernej Ule, Emmanouil Metzakopian, Marc-David Ruepp, Giovanna R. Mallucci

Summary: Enhanced expression of the cold-shock protein RBM3 is neuroprotective. A CRISPR-Cas9 knockout screen identified splicing factors that regulate RBM3 levels, with HNRNPH1 being the strongest positive regulator. Moderate hypothermia represses inclusion of a poison exon via HNRNPH1's thermosensitive interaction with a G-rich motif. The study provides mechanistic insights into RBM3 regulation and potential therapeutic targets for neuroprotection.

EMBO JOURNAL (2023)

添加到收藏夹
Article Biochemistry & Molecular Biology

An ERK1/2-driven RNA-binding switch in nucleolin drives ribosome biogenesis and pancreatic tumorigenesis downstream of RAS oncogene

Muhammad S. Azman, Emilie L. Alard, Martin Dodel, Federica Capraro, Rupert Faraway, Maria Dermit, Wanling Fan, Alina Chakraborty, Jernej Ule, Faraz K. Mardakheh

Summary: Oncogenic RAS signaling reshapes the RNA-bound proteomic landscape of pancreatic cancer cells, enhancing the RNA-binding activity of nucleolin. This process promotes ribosome biogenesis, crucial for RAS-induced pancreatic cancer cell proliferation, and can be targeted therapeutically to inhibit tumor growth. Our findings highlight the role of nucleolin in RAS-mediated tumorigenesis and provide insights into the post-transcriptional mechanism of RAS in modulating gene expression.

EMBO JOURNAL (2023)

添加到收藏夹
Article Biochemistry & Molecular Biology

3D Visualization, Skeletonization and Branching Analysis of Blood Vessels in Angiogenesis

Vignesh Ramakrishnan, Rebecca Schoenmehl, Annalena Artinger, Lina Winter, Hendrik Boeck, Stephan Schreml, Florian Guertler, Jimmy Daza, Volker H. Schmitt, Andreas Mamilos, Pablo Arbelaez, Andreas Teufel, Tanja Niedermair, Ondrej Topolcan, Marie Karlikova, Samuel Sossalla, Christoph B. Wiedenroth, Markus Rupp, Christoph Brochhausen

Summary: In this paper, a pipeline of vision algorithms is proposed to visualize and analyze 3D blood vessels from tissue samples. The technique involves blood vessel segmentation using a U-net neural network, image registration for alignment, and branching analysis using a skeletonization algorithm. This method is useful for researchers, pathologists, and doctors in understanding vascular morphogenesis and potential diagnostic applications under different pathophysiological conditions.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

添加到收藏夹
Article Biochemistry & Molecular Biology

Molecular and Functional Relevance of Na(V)1.8-Induced Atrial Arrhythmogenic Triggers in a Human SCN10A Knock-Out Stem Cell Model

Nico Hartmann, Maria Knierim, Wiebke Maurer, Nataliya Dybkova, Gerd Hasenfuss, Samuel Sossalla, Katrin Streckfuss-Boemeke

Summary: In heart failure and atrial fibrillation, a persistent Na+ current (I-NaL) exerts detrimental effects on cellular electrophysiology and can induce arrhythmias. Na(V)1.8 contributes to arrhythmogenesis by inducing I-NaL. Mutations in the SCN10A gene (Na(V)1.8) are associated with increased risk for arrhythmias, Brugada syndrome, and sudden cardiac death. The mediation of these Na(V)1.8-related effects is still a subject of controversial discussion.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

添加到收藏夹
Editorial Material Biochemistry & Molecular Biology

Looping in on splicing CRIC-seq uncovers PTBP1's long-range RNA regulatory rules

Ira Alexandra Iosub, Tajda Klobuc, Jernej Ule

Summary: RNA looping plays a crucial role in understanding the regulatory mechanisms of protein-RNA interactions. Xue et al. introduce CRIC-seq, a comprehensive method to identify RNA loops mediated by specific proteins, and demonstrate their significance in interpreting disease-causing mutations.

MOLECULAR CELL (2023)

添加到收藏夹
Article Biochemistry & Molecular Biology

A computationally-enhanced hiCLIP atlas reveals Staufen1-RNA binding features and links 3′ UTR structure to RNA metabolism

Anob M. Chakrabarti, Ira A. Iosub, Flora C. Y. Lee, Jernej Ule, Nicholas M. Luscombe

Summary: The structure of mRNA molecules plays a crucial role in its interactions with RNA binding proteins (RBPs), but current experimental methods for studying these interactions are limited in sensitivity. In this study, the researchers extended the hiCLIP atlas of STAU1-bound duplexes by 10-fold through improved experimental assumptions and computational methods. They developed a computational pipeline called Tosca for processing and analyzing proximity ligation sequencing data, and used it to gain insights into the RNA selectivity of STAU1 and the effects of RBP-RNA structure interactions.

NUCLEIC ACIDS RESEARCH (2023)

添加到收藏夹
Article Endocrinology & Metabolism

Basal re-esterification finetunes mitochondrial fatty acid utilization

Anand Kumar Sharma, Tongtong Wang, Alaa Othman, Radhika Khandelwal, Miroslav Balaz, Salvatore Modica, Nicola Zamboni, Christian Wolfrum

Summary: Emerging evidence suggests the existence of constant basal lipolysis and re-esterification of fatty acids. In this study, the role of lipolysis coupled to re-esterification under basal conditions was investigated. The results showed that DGAT1 and DGAT2 mediated re-esterification plays a role in regulating fatty acid oxidation and mitochondrial fuel utilization.

MOLECULAR METABOLISM (2023)

添加到收藏夹
Article Multidisciplinary Sciences

Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells

Francesco Petrelli, Valentina Scandella, Sylvie Montessuit, Nicola Zamboni, Jean-Claude Martinou, Marlen Knobloch

Summary: Cellular metabolism plays a crucial role in the behavior of adult neural stem/progenitor cells (NSPCs). The mitochondrial pyruvate carrier (MPC) is identified as an important factor in controlling NSPC quiescence and activation.

SCIENCE ADVANCES (2023)

添加到收藏夹
Article Endocrinology & Metabolism

Metabolic landscape of the male mouse gut identifies different niches determined by microbial activities

Karin H. U. Meier, Julian Trouillon, Hai Li, Melanie Lang, Tobias Fuhrer, Nicola Zamboni, Shinichi Sunagawa, Andrew J. Macpherson, Uwe Sauer

Summary: Anatomically resolved maps of small molecules reveal distinct spatial patterns throughout the gut of colonized and germ-free mice, which can be associated with specific microorganisms. The map of the longitudinal metabolome in the gut of healthy mice shows a shift from amino acids to organic acids, vitamins, and nucleotides along the gut. Comparisons between colonized and germ-free mice help identify the origin of metabolites and suggest specific microbial influence on the metabolome.

NATURE METABOLISM (2023)

添加到收藏夹
Article Cardiac & Cardiovascular Systems

A Pilot Trial to Compare the Long-Term Efficacy of Pulmonary Vein Isolation with High-Power Short-Duration Radiofrequency Versus Laser Energy with Rapid Ablation Mode

Soenke Schildt, Sabine Fredersdorf, Carsten G. Jungbauer, Christian Hauck, Daniel Tarnowski, Kurt Debl, Stefan Neef, Christian Schach, Samuel Sossalla, Lars S. Maier, Ekrem Uecer

Summary: This observational pilot trial compared the efficacy of high-power short-duration radiofrequency energy (HPSD) and the visually guided laser balloon (VGLB) in pulmonary vein isolation (PVI) and found no difference in long-term outcome. A large randomized study is needed to compare the clinical outcomes of these new ablation techniques.

JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE (2023)

添加到收藏夹
Article Biotechnology & Applied Microbiology

Towards in silico CLIP-seq: predicting protein-RNA interaction via sequence-to-signal learning

Marc Horlacher, Nils Wagner, Lambert Moyon, Klara Kuret, Nicolas Goedert, Marco Salvatore, Jernej Ule, Julien Gagneur, Ole Winther, Annalisa Marsico

Summary: RBPNet is a new deep learning method that predicts CLIP-seq crosslink count distribution from RNA sequence. Training on millions of regions, RBPNet shows high generalization on eCLIP, iCLIP, and miCLIP assays, outperforming state-of-the-art classifiers. RBPNet performs bias correction by modeling the raw signal as a mixture of protein-specific and background signal. By using Integrated Gradients for model interrogation, RBPNet identifies predictive sub-sequences corresponding to known and novel binding motifs and enables variant-impact scoring through in silico mutagenesis. Overall, RBPNet improves the imputation of protein-RNA interactions and enhances mechanistic interpretation of predictions.

GENOME BIOLOGY (2023)

添加到收藏夹
Article Biochemical Research Methods

Regularized adversarial learning for normalization of multi-batch untargeted metabolomics data

Andrei Dmitrenko, Michelle Reid, Nicola Zamboni

Summary: We propose a new method, RALPS, for the normalization of multi-batch untargeted metabolomics data using deep adversarial learning. RALPS outperforms six state-of-the-art methods for batch correction, preserving biological identity, spectral properties, and coefficients of variation. It demonstrates good scalability, robustness, ability to handle missing values, and adaptability to different experimental designs.

BIOINFORMATICS (2023)

添加到收藏夹
暂无数据
研讨会 海报 问题 讨论圈 基金 期刊 论文 科研社交 资讯集成 审稿人 关于我们 常见问题 移动App 隐私条款 使用条款
© Peeref 2019-2024. All rights reserved.