☆ 4.8 Article

p38 MAPK Controls Prothrombin Expression by Regulated RNA 3′ End Processing

MOLECULAR CELL (2011)

获取全文
添加到收藏夹

期刊

MOLECULAR CELL
卷 41, 期 3, 页码 298-310

出版社

CELL PRESS
DOI: 10.1016/j.molcel.2010.12.032

关键词

-

类别

Biochemistry & Molecular Biology Cell Biology

资金

  1. University of Heidelberg
  2. Deutsche Forschungsgemeinschaft
  3. Fritz-Thyssen Stiftung
  4. DFG Forschergruppe [FOR 426]
  5. Lautenschlager Research Prize

向作者/读者索取更多资源

Protocol

社区支持

Reagent

社区支持

Thrombin is a key protease involved in blood coagulation, complement activation, inflammation, angiogenesis, and tumor invasion. Although induced in many (patho-)physiological conditions, the underlying mechanisms controlling prothrombin expression remained enigmatic. We have now discovered that prothrombin expression is regulated by a post-transcriptional regulatory mechanism responding to stress and inflammation. This mechanism is triggered by external stimuli that activate p38 MAPK. In turn, p38 MAPK upmodulates canonical 3' end processing components and phosphorylates the RNA-binding proteins FBP2 and FBP3, which inhibit 3' end processing of mRNAs, such as prothrombin mRNA, that bear a defined upstream sequence element (USE) in their 3'UTRs. Upon phosphorylation, FBP2 and FBP3 dissociate from the USE, making it accessible to proteins that stimulate 3' end processing. We provide in vivo evidence suggesting the importance of this mechanism in inflammatory hypercoagulation and tumor invasion. Regulated 3' end processing thus emerges as a key mechanism of gene regulation with broad biological and medical implications.

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

Review Genetics & Heredity

RNA-binding proteins in human genetic disease

Fatima Gebauer, Thomas Schwarzl, Juan Valcarcel, Matthias W. Hentze

Summary: RNA-binding proteins (RBPs) are key effectors of gene expression, and their malfunction leads to various diseases. RBPs play important roles in human genetic disorders, with emerging therapeutic interventions targeting RBPs.

NATURE REVIEWS GENETICS (2021)

添加到收藏夹
Article Cell Biology

Identification of dynamic RNA-binding proteins uncovers a Cpeb4-controlled regulatory cascade during pathological cell growth of cardiomyocytes

Eva Riechert, Vivien Kmietczyk, Frank Stein, Thomas Schwarzl, Thileepan Sekaran, Lonny Juergensen, Verena Kamuf-Schenk, Eshita Varma, Christoph Hofmann, Mandy Rettel, Kira Guer, Julie Oelschlaeger, Friederike Kuehl, Judit Martin, Marta Ramirez-Pedraza, Mercedes Fernandez, Shirin Doroudgar, Raul Mendez, Hugo A. Katus, Matthias W. Hentze, Mirko Voelkers

Summary: RNA-binding proteins (RBPs) play a critical role in controlling cardiomyocyte function, and the cytoplasmic polyadenylation element-binding protein 4 (Cpeb4) is identified as a key regulator of cardiac growth and remodeling by differential binding to specific mRNAs. This study reveals a system-wide view of active RBPs in cardiomyocytes during growth response, shedding light on their role in regulating cardiomyocyte function.

CELL REPORTS (2021)

添加到收藏夹
Article Immunology

Listening to the Whispers in Neuroimmune Crosstalk: A Comprehensive Workflow to Investigate Neurotrophin Receptor p75NTR Under Endogenous, Low Abundance Conditions

Benjamin W. Dorschner, Ralf Wiedemuth, Ann-Christin Funke, Marc Gentzel, Mary-Louise Rogers, Sebastian Brenner, Sebastian Thieme

Summary: This study introduces a comprehensive workflow and an optimized IP protocol for investigating neurotrophin receptor p75NTR at endogenous, low abundance levels, providing detailed instructions from lysate preparation to successful detection of protein-protein interactions.By utilizing human melanoma cell line A375 and human leukemic plasmacytoid dendritic cell line PMDC05, specific antibodies and IP conditions were validated, revealing 14-3-3 epsilon:p75NTR interactions.

FRONTIERS IN IMMUNOLOGY (2021)

添加到收藏夹
Article Genetics & Heredity

CD27 expression on Treg cells limits immune responses against tumors

Sabine Muth, Annekatrin Klaric, Markus Radsak, Hansjoerg Schild, Hans Christian Probst

Summary: Treg-expressed CD27 maintains DC tolerogenic in steady state and limits anti-tumor immunity; Ablation of Treg-expressed CD27 synergizes with PD-1 blockade to improve CTL-mediated tumor control.

JOURNAL OF MOLECULAR MEDICINE-JMM (2022)

添加到收藏夹
Article Hematology

Constitutional PIGA mutations cause a novel subtype of hemochromatosis in patients with neurologic dysfunction

Lena Muckenthaler, Oriana Marques, Silvia Colucci, Joachim Kunz, Piotr Fabrowski, Thomas Bast, Sandro Altamura, Britta Hochsmann, Hubert Schrezenmeier, Monika Langlotz, Paulina Richter-Pechanska, Tobias Rausch, Nicole Hofmeister-Mielke, Nikolas Gunkel, Matthias W. Hentze, Andreas E. Kulozik, Martina U. Muckenthaler

BLOOD (2022)

添加到收藏夹
Article Plant Sciences

Shedding light on silica biomineralization by comparative analysis of the silica-associated proteomes from three diatom species

Alastair W. Skeffington, Marc Gentzel, Andre Ohara, Alexander Milentyev, Christoph Heintze, Lorenz Boettcher, Stefan Goerlich, Andrej Shevchenko, Nicole Poulsen, Nils Kroeger

Summary: This study extracted silica proteins from three diatom species and found that there were no common proteins among them, and most proteins showed low similarity in sequence alignments. Bioinformatic analysis grouped these proteins into different classes based on unconventional sequence motifs, but their functions are still unclear. In vivo localization results of selected proteins suggest that proteins lacking sequence homology but sharing unconventional sequence motifs may have similar functions in diatom silica cell wall morphogenesis.

PLANT JOURNAL (2022)

添加到收藏夹
Article Biochemistry & Molecular Biology

Vault RNA1-1 riboregulates the autophagic function of p62 by binding to lysine 7 and arginine 21, both of which are critical for p62 oligomerization

Magdalena Buescher, Rastislav Horos, Ina Huppertz, Kevin Haubrich, Nikolay Dobrev, Florence Baudin, Janosch Hennig, Matthias W. Hentze

Summary: This study reveals the mechanism by which vault RNA1-1 inhibits the oligomerization of p62 through biochemical and functional experiments. The PB1 domain and adjacent linker region of p62 (aa 1-122) are identified as critical for specific binding with vault RNA1-1, and lysine 7 and arginine 21 are identified as key hinges for p62 riboregulation. Additionally, chemical structure probing of vault RNA1-1 identifies a central flexible loop that is required for the specific interaction with p62.

RNA (2022)

添加到收藏夹
Article Biochemistry & Molecular Biology

Riboregulation of Enolase 1 activity controls glycolysis and embryonic stem cell differentiation

Ina Huppertz, Joel I. Perez-Perri, Panagiotis Mantas, Thileepan Sekaran, Thomas Schwarzl, Francesco Russo, Dunja Ferring-Appel, Zuzana Koskova, Lyudmila Dimitrova-Paternoga, Eleni Kafkia, Janosch Hennig, Pierre A. Neveu, Kiran Patil, Matthias W. Hentze

Summary: The study reveals acetylation-driven riboregulation of ENO1 as a physiological mechanism of glycolytic control and stem cell differentiation regulation, providing new insights into the differentiation of stem cell metabolism and fate trajectories.

MOLECULAR CELL (2022)

添加到收藏夹
Article Dermatology

Topical Application of Adenosine A2-Type Receptor Agonists Prevents Contact Hypersensitivity Reactions in Mice by Affecting Skin Dendritic Cells

Cinthia Silva-Vilches, Vanessa Bolduan, Mohamad Alabdullah, Kerstin Steinbrink, Hans Christian Probst, Alexander Enk, Karsten Mahnke

Summary: Ado receptor agonists applied topically to the skin can reduce swelling and activation of T cells during contact hypersensitivity reactions. In lymph nodes, the treatment with CGS leads to increased numbers of T cells expressing anergic markers. After sensitization, the Ado receptor agonists also reduce the production of proinflammatory cytokines and chemokines in ear tissue, as well as the infiltration of neutrophils.

JOURNAL OF INVESTIGATIVE DERMATOLOGY (2023)

添加到收藏夹
Article Biochemistry & Molecular Biology

Small noncoding RNA interactome capture reveals pervasive, carbon source-dependent tRNA engagement of yeast glycolytic enzymes

Claudio Asencio, Thomas Schwarzl, Sudeep Sahadevan, Matthias W. Hentze

Summary: Small noncoding RNAs play important roles in cellular and organismal biology, working with RNA-binding proteins (RBPs). In order to specifically identify RBPs binding to small noncoding RNAs, a method called small noncoding RNA interactome capture (snRIC(2C)) was developed. Through this method, nearly 300 proteins that specifically bind to RNAs smaller than 200 nt in length (snRBPs) were identified, revealing differences from the total RNA-binding proteome. Further analysis showed that most glycolytic enzymes from yeast are snRBPs, and tRNA engagement of the glycolytic enzyme GAPDH is carbon source-dependent and regulated by the RNA polymerase III repressor Maf1, suggesting a regulatory interaction between glycolysis and RNA polymerase III activity. This study demonstrates the effectiveness of snRIC(2C) and other 2C-derived methods in studying RBPs and uncovering previously unrecognized interactions.

RNA (2023)

添加到收藏夹
Article Multidisciplinary Sciences

The RNA-binding protein landscapes differ between mammalian organs and cultured cells

Joel I. Perez-Perri, Dunja Ferring-Appel, Ina Huppertz, Thomas Schwarzl, Sudeep Sahadevan, Frank Stein, Mandy Rettel, Bruno Galy, Matthias W. Hentze

Summary: The eRIC method was used to characterize the RNA-bound proteomes of three different mouse organs, revealing over 1300 active RNA-binding proteins, with nearly a quarter being previously unknown. Systematic differences in RNA binding were also observed between organs and cultured cells.

NATURE COMMUNICATIONS (2023)

添加到收藏夹
Article Cardiac & Cardiovascular Systems

Translational control of Ybx1 expression regulates cardiac function in response to pressure overload in vivo

Eshita Varma, Jana Burghaus, Thomas Schwarzl, Thileepan Sekaran, Parul Gupta, Agnieszka A. Gorska, Christoph Hofmann, Claudia Stroh, Lonny Juergensen, Verena Kamuf-Schenk, Xue Li, Rebekka Medert, Florian Leuschner, Vivien Kmietczyk, Marc Freichel, Hugo A. Katus, Matthias W. Hentze, Norbert Frey, Mirko Voelkers

Summary: RNA-protein interactions are important for cardiac function, but the regulation of individual RNA-binding proteins through signaling cascades during heart failure development is not well understood. The study found that mTOR signaling is linked to the upregulation of the RNA-binding protein Ybx1, which is involved in cardiac hypertrophy by regulating protein synthesis. The depletion of Ybx1 preserved heart function during pathological cardiac hypertrophy.

BASIC RESEARCH IN CARDIOLOGY (2023)

添加到收藏夹
Article Biochemical Research Methods

htseq-clip: a toolset for the preprocessing of eCLIP/iCLIP datasets

Sudeep Sahadevan, Thileepan Sekaran, Nadia Ashaf, Marko Fritz, Matthias W. Hentze, Wolfgang Huber, Thomas Schwarzl

Summary: Transcriptome-wide detection of binding sites of RNA-binding proteins can be achieved using Individual-nucleotide crosslinking and immunoprecipitation (iCLIP) and its derivative enhanced CLIP (eCLIP) sequencing methods. The python package htseq-clip is introduced for preprocessing, extracting, and summarizing crosslink site counts from i/eCLIP experimental data. The package provides crosslink site count matrices and other metrics for filtering and downstream analyses, such as the identification of differential binding sites.

BIOINFORMATICS (2023)

添加到收藏夹
Article Biochemistry & Molecular Biology

Improved discovery of RNA-binding protein binding sites in eCLIP data using DEWSeq

Thomas Schwarzl, Sudeep Sahadevan, Benjamin Lang, Milad Miladi, Rolf Backofen, Wolfgang Huber, Matthias W. Hentze, Gian Gaetano Tartaglia

Summary: Enhanced crosslinking and immunoprecipitation sequencing (eCLIP-seq) is a method for detecting RNA-binding protein binding sites. However, current analysis strategies have low replication and high false positive rates. DEWSeq, a R/Bioconductor package, improves the detection of binding regions by utilizing replicate information and size-matched input controls. It has been shown to significantly increase the number and quality of binding sites.

NUCLEIC ACIDS RESEARCH (2023)

添加到收藏夹
Letter Hematology

Iron-dependent BMP6 Regulation in Liver Sinusoidal Endothelial Cells Is Instructed by Hepatocyte-derived Secretory Signals

Silvia Colucci, Sandro Altamura, Oriana Marques, Katja Muedder, Anand R. Agarvas, Matthias W. Hentze, Martina U. Muckenthaler

HEMASPHERE (2022)

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.