Article
Cell Biology
Poulomi Banerjee, Shubha Markande, Misha Kalarikkal, Jomon Joseph
Summary: Nuclear export of mRNAs is a crucial step in eukaryotic gene expression. This study reveals that DDX19 gets covalently attached with SUMO at lysine 26, which enhances its interaction with Gle1 and fine-tunes its function in mRNA export.
JOURNAL OF CELL SCIENCE
(2022)
Article
Multidisciplinary Sciences
Cristina Leoni, Marian Bataclan, Taku Ito-Kureha, Vigo Heissmeyer, Silvia Monticelli
Summary: This study investigates the role of m(6)A mRNA methyltransferase complex in mast cells and its impact on mast cell proliferation and survival. Depletion of the catalytic component Metll3 exacerbates effector functions and leads to enhanced expression of inflammatory cytokines in response to IgE and antigen complexes. It is found that the IL-13 cytokine encoding mRNA is methylated in activated mast cells and that Metll3 affects its transcript stability in an enzymatic activity-dependent manner.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Yihu Xie, Bradley P. Clarke, Yong Joon Kim, Austin L. Ivey, Pate S. Hill, Yi Shi, Yi Ren
Summary: The TREX complex, composed of THO sub-complex and Sub2 ATPase, plays central roles in mRNP maturation and export. The THO complex stabilizes the semi-open conformation of Sub2 and interacts extensively with the SR-like protein Gbp2 to facilitate its loading onto mRNP.
Article
Medicine, Research & Experimental
Huan Wang, Tracey W. Chan, Ajay A. Vashisht, Brian G. Drew, Anna C. Calkin, Thurl E. Harris, James A. Wohlschlegel, Xinshu Xiao, Karen Reue
Summary: Lipin 1 regulates cellular lipid homeostasis through roles in glycerolipid synthesis and transcriptional coactivation, but its deficiency can lead to episodic disease symptoms triggered by metabolic stress. Fasting exacerbates the deleterious effects of lipin 1 deficiency on metabolic homeostasis, mainly through its influence on mRNA splicing in the liver.
Article
Biochemistry & Molecular Biology
Zhiling Kuang, Jiyuan Ke, Jiong Hong, Zhongliang Zhu, Liwen Niu
Summary: PCI domain proteins play important roles in post-transcriptional gene regulation. In this study, the structure of yeast Thp3-Csn12-Sem1 ternary complex was determined, revealing significant structural differences compared to the Sac3-Thp1-Sem1 complex. This structure provides a foundation for further exploring its specific recruitment to the spliceosome.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ines Caetano, Sonia Ferreira, Ana Coelho, Liliana Amorim, Teresa Costa Castanho, Carlos Portugal-Nunes, Jose Miguel Soares, Nuno Goncalves, Rui Sousa, Joana Reis, Catarina Lima, Paulo Marques, Pedro Silva Moreira, Ana Joao Rodrigues, Nadine Correia Santos, Pedro Morgado, Ricardo Magalhaes, Maria Pico-Perez, Joana Cabral, Nuno Sousa
Summary: The association between stress and psychiatric disorders has prompted research on stress's impact on the brain. In this study, perceived stress was found to be directly associated with increased connectivity between the amygdala and frontal cortical regions, indicating that stress may lead to altered functional connectivity patterns.
MOLECULAR PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Zhicong Zhao, Ying Qing, Lei Dong, Li Han, Dong Wu, Yangchan Li, Wei Li, Jianhuang Xue, Keren Zhou, Miao Sun, Brandon Tan, Zhenhua Chen, Chao Shen, Lei Gao, Andrew Small, Kitty Wang, Keith Leung, Zheng Zhang, Xi Qin, Xiaolan Deng, Qiang Xia, Rui Su, Jianjun Chen
Summary: The mRNA internal m7G modification is recognized by Quaking proteins (QKIs), which regulate mRNA stability and translation, affecting cellular drug resistance.
Article
Multidisciplinary Sciences
Renata Naporano Bicev, Maximilia Frazao de Souza Degenhardt, Cristiano Luis Pinto de Oliveira, Emerson Rodrigo da Silva, Jeril Degrouard, Guillaume Tresset, Graziella Eliza Ronsein, Marilene Demasi, Fernanda Marques da Cunha
Summary: Glucose restriction enhances the activity of proteasomes in yeast cells, improving their ability to degrade proteins, possibly through phosphorylation of the proteasome subunit. However, this enhancement in activity does not result from changes in the conformation of the proteasome particles.
SCIENTIFIC REPORTS
(2023)
Article
Microbiology
Zijian Guo, Yuanyuan He, Jian Xu, Ananya N. Benegal, Steven L. Brody, Michael D. Vahey
Summary: By tracking the spread of influenza virus from single infected cells, it was found that the surface protein neuraminidase (NA) plays a key role in controlling cellular coinfection. NA depletes viral receptors from infected and neighboring uninfected cells. In cases of low viral infectious potential, inhibition of NA increases the local spread of infection by increasing the viral load received by neighboring cells.
Article
Microbiology
Ross Hall, Anabel Guedan, Melvyn W. Yap, George R. Young, Ruth Harvey, Jonathan P. Stoye, Kate N. Bishop
Summary: This study reveals how SARS-CoV-2 suppresses cellular protein production by interacting with cellular protein Rae1 and blocking mRNA export. It provides new insights into the replication strategies of SARS-CoV-2 and its manipulation of the host cell environment.
Article
Biochemistry & Molecular Biology
Sayaka Dantsuji, Mutsuhito Ohno, Ichiro Taniguchi
Summary: In eukaryotic cells, different classes of RNAs are exported to the cytoplasm by specific factors. Previous studies have shown that RNA polymerase II transcripts are classified based on their length, and hnRNP C is a key factor in this classification process. hnRNP C inhibits the recruitment of PHAX to long transcripts, but the mechanisms behind this inhibition are still unknown.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Jie Cheng, Peng Zhao, Lin Zhu, Fang Zhu, Zhiqiang Tian, Zhongjian Shen, Xiaoming Liu, Xiaoxia Liu
Summary: In this study, the neuropeptide Corazonin (Crz) and its receptor were characterized in Grapholita molesta, and their role in regulating copulation duration and fertility in males was investigated. Knockdown of Crz or its receptor led to prolonged copulation duration and decreased fertility in males without affecting sperm production. The knockdown also resulted in significantly diminished levels of accessory gland proteins and downregulation of genes involved in serine-type endopeptidase activity in the accessory gland. Furthermore, disruption of sperm activation in the spermatophore of females mated with knockdown males was observed. These findings provide new insights into the functions of Crz signaling in Lepidopteran insects.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Yiyang Xu, Guping Mao, Dianbo Long, Zengfa Deng, Ruobin Xin, Ziji Zhang, Ting Xue, Weiming Liao, Jie Xu, Yan Kang
Summary: This study found that a circular RNA called circCREBBP is highly expressed in cartilage samples taken from individuals with osteoarthritis, and it induces destruction of the surrounding extracellular matrix through its inhibitory effects on a microRNA. Inhibiting circCREBBP activity prevented cartilage breakdown and alleviated osteoarthritis in mouse models, suggesting that it could be a potential therapeutic target for treating osteoarthritis.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Sebastian Grosse, Yen-Yun Lu, Ivo Coban, Bettina Neumann, Heike Krebber
Summary: This study revealed that Gbp2 and Hrb1 are involved in nonsense mediated decay of premature termination codon-containing mRNAs by forming a complex with Upf proteins. They aid in transmitting PTC recognition signals and promoting translation repression and RNA degradation, thus controlling mRNA quality beyond the nuclear border. Identification of SR proteins as global surveillance factors in yeast sheds light on their potential role in understanding the complex human system with diseases related to defects in SR proteins or NMD.
Article
Biochemistry & Molecular Biology
Kamilla Gomori, Melissa Herwig, Roua Hassoun, Heidi Budde, Nusratul Mostafi, Simin Delalat, Suvasini Modi, Merima Begovic, Tamara Szabados, Judit Pipis, Nikolett Farkas-Morvay, Istvan Lepran, Arpad Kovacs, Andreas Mugge, Peter Ferdinandy, Aniko Gorbe, Peter Bencsik, Nazha Hamdani
Summary: This study investigates the effects of volume overload on the heart using a rat model and finds that it leads to cardiac hypertrophy, mechanical dysfunction, dysregulated signaling pathways, and increased oxidative stress. Furthermore, oxidative stress causes impairment of the protein quality control system.
Review
Biochemistry & Molecular Biology
Jan Keiten-Schmitz, Linda Roder, Eran Hornstein, Michaela Muller-McNicoll, Stefan Muller
Summary: The spatial organization of cellular processes in membranous or membrane-less organelles is crucial for compartmentalizing biochemical pathways. Molecular condensates, such as the nucleolus and nuclear bodies, are enriched in intrinsically disordered proteins and RNA and are formed through liquid-liquid phase separation. Changes in the dynamics of these organelles play a major role in cell dysfunction and disease, with post-translational modifications, such as the SUMO system, regulating their assembly and disassembly.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Javier Larrasa-Alonso, Maria Villalba-Orero, Carlos Marti-Gomez, Paula Ortiz-Sanchez, Marina M. Lopez-Olaneta, M. Ascension Rey-Martin, Fatima Sanchez-Cabo, Francois McNicoll, Michaela Muller-McNicoll, Pablo Garcia-Pavia, Enrique Lara-Pezzi
Summary: RBP SRSF4 plays a critical role in the heart, with its loss of expression leading to cardiac hypertrophy, diastolic dysfunction, and abnormal repolarization. The mechanism involves downregulation of GAS5 and subsequent elevation of GR transcriptional activity. These findings may contribute to the development of new therapeutic approaches for cardiac hypertrophy and myocardial pathology in patients with Cushing syndrome.
CIRCULATION RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Irena Sliskovic, Hannah Eich, Michaela Muller-McNicoll
Summary: Members of the SR protein family are multifunctional RNA-binding proteins that play key roles in mRNP formation and splicing. In addition to their essential roles in constitutive and alternative splicing, SR proteins have been reported to have many other activities. Studying the versatility of SR proteins poses challenges, but specific approaches can be used to unravel their activities, which can be applied to other multifunctional RBPs as well.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Oncology
Eiman Elwakeel, Mirko Brueggemann, Jessica Wagih, Olga Lityagina, Mohammed A. F. Elewa, Yingying Han, Timo Froemel, Ruediger Popp, Adele M. Nicolas, Yannick Schreiber, Elise Gradhand, Dominique Thomas, Rolf Nuesing, Julia Steinmetz-Spaeh, Rajkumar Savai, Emmanouil Fokas, Ingrid Fleming, Florian R. Greten, Kathi Zarnack, Bernhard Bruene, Andreas Weigert
Summary: Prostaglandin E2 has a paradoxical role in cancer-associated fibroblast activation and tumor progression, as it restricts primary tumor growth while promoting metastasis.
Article
Biochemistry & Molecular Biology
Rebekka Bauer, Sofie Patrizia Meyer, Karolina Anna Kloss, Vanesa Maria Guerrero Ruiz, Samira Reuscher, You Zhou, Dominik Christian Fuhrmann, Kathi Zarnack, Tobias Schmid, Bernhard Bruene
Summary: This study comprehensively investigated the impact of hypoxia on mRNA expression, transcription, and mRNA stability, revealing that mRNA destabilization becomes more important under chronic hypoxia, controlling mitochondrial functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jan-Niklas Tants, Lea Marie Becker, Francois McNicoll, Michaela Mueller-McNicoll, Andreas Schlundt
Summary: This study provides the secondary structure of mRNA 3'UTR for the first time and investigates the functional and structural integration of multiple elements in 3'UTR regulatory hubs. The binding of Roquin protein to decay elements depends on their structural embedment. The research highlights the significance of studying RNA regulation in a full sequence and structural context.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
S. Engelhardt, S. Dimmeler, C. Heim, C. Baer, T. Boettger, R. Boon, R. P. Brandes, T. Braun, A. Dueck, J. Gagneur, P. Grote, L. M. Holdt, N. Jae, J. Krishnan, C. Kupatt, K. -l. Laugwitz, M. S. Leisegang, L. Maegdefessel, T. Meitinger, A. Moretti, M. Mueller-McNicoll, M. Sattler, A. Schnieke, M. Schulz, H. Schunkert, H. Schwalbe, D. Teupser, T. Thum, C. Weber, I. Wittig, K. Zarnack
Summary: The discovery of regulatory noncoding RNA molecules has revolutionized our understanding of gene expression. These RNA molecules, especially microRNAs, long noncoding RNAs, and circular RNAs, play important roles in the cardiovascular system and have potential for therapeutic applications. However, the complexity of RNA transcripts and the mechanisms of their actions present significant challenges for further research.
Article
Multidisciplinary Sciences
Alisha N. Jones, Carina Grass, Isabel Meininger, Arie Geerlof, Melina Klostermann, Kathi Zarnack, Daniel Krappmann, Michael Sattler
Summary: This study shows that alternative splicing of MALT1 depends on RNA structural elements that sequester the splice sites of the alternatively spliced exon7, and is regulated by competitive binding of RBPs hnRNP U and hnRNP L.
Article
Multidisciplinary Sciences
Mariela Cortes-Lopez, Laura Schulz, Mihaela Enculescu, Claudia Paret, Bea Spiekermann, Mathieu Quesnel-Vallieres, Manuel Torres-Diz, Sebastian Unic, Anke Busch, Anna Orekhova, Monika Kuban, Mikhail Mesitov, Miriam M. Mulorz, Rawan Shraim, Fridolin Kielisch, Joerg Faber, Yoseph Barash, Andrei Thomas-Tikhonenko, Kathi Zarnack, Stefan Legewie, Julian Koenig
Summary: After CART-19 immunotherapy for B-cell acute lymphoblastic leukaemia (B-ALL), relapse often occurs due to loss of the CD19 epitope. The study investigated the regulatory code that controls CD19 splicing and identified mutations and splice isoforms that could contribute to CART-19 resistance in B-ALL patients. Additionally, regulatory elements and RNA-binding proteins that control CD19 splicing were identified, highlighting their importance in CD19 mis-splicing.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Camila de Oliveira Freitas Machado, Michal Schafranek, Mirko Brueggemann, Maria Clara Hernandez Canas, Mario Keller, Antonella Di Liddo, Andre Brezski, Nicole Bluemel, Benjamin Arnold, Anja Bremm, Ilka Wittig, Nicolas Jae, Francois McNicoll, Stefanie Dimmeler, Kathi Zarnack, Michaela Mueller-McNicoll
Summary: Hypoxia triggers significant changes in alternative splicing, and the splicing factor SRSF6 plays a crucial role in this response by regulating the inclusion of a poison cassette exon (PCE) through SRSF4. The reduction of SRSF6 levels in acute hypoxia promotes the dispersal of nuclear speckles, leading to the reprogramming of gene expression and hypoxic adaptation. Aberrantly high SRSF6 expression in hypoxia negatively affects alternative splicing and nuclear speckle dispersal, resulting in increased proliferation, genomic instability, and suppressed stress response. The SRSF4-PCE-SRSF6 hypoxia axis is active in different types of cancer, and high expression of SRSF6 in hypoxic tumors is associated with poor prognosis.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Philipp Keil, Alexander Wulf, Nitin Kachariya, Samira Reuscher, Kristin Huhn, Ivan Silbern, Janine Altmuller, Mario Keller, Ralf Stehle, Kathi Zarnack, Michael Sattler, Henning Urlaub, Katja Straesser
Summary: RNA-binding proteins (RBPs) control RNA metabolism through protein-RNA and protein-protein interactions. In this study, we identified in vivo RNA crosslinks in nuclear mRNP components and functionally analyzed the Npl3 protein. Mutations in the RNA recognition motifs (RRMs) and linker region of Npl3 revealed distinct functions of different RNA-binding domains. Importantly, a linker mutation impaired mRNP assembly, revealing a previously unknown function of Npl3. This integrative analysis can be applied to study RBPs in other RNA metabolic processes.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Lena Molitor, Melina Klostermann, Sabrina Bacher, Juliane Merl-Pham, Nadine Spranger, Sandra Burczyk, Carolin Ketteler, Ejona Rusha, Daniel Tews, Anna Pertek, Marcel Proske, Anke Busch, Sarah Reschke, Regina Feederle, Stefanie M. Hauck, Helmut Blum, Micha Drukker, Pamela Fischer-Posovszky, Julian Koenig, Kathi Zarnack, Dierk Niessing
Summary: The RNA-binding protein PURA is predominantly located in the cytoplasm, where it binds to thousands of mRNAs. Reduced levels of PURA affect the formation and composition of P-bodies, leading to dysregulation of RNA processing. This study proposes PURA Syndrome as a new model for studying the connection between P-body-associated RNA regulation and neurodevelopmental disorders.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Luisa Kirchhof, Youssef Fouani, Andrea Knau, Galip S. Aslan, Andreas W. Heumueller, Ilka Wittig, Michaela Mueller-McNicoll, Stefanie Dimmeler, Nicolas Jae
Summary: This study identifies lncRNA CALA as a crucial regulator of RNA decay in endothelial cells, forming cytoplasmic ribonucleoprotein complexes with G3BP1 and affecting endothelial cell functions. The study also reveals the association between G3BP1 and various NMD factors, which is CALA-dependent. Silencing of CALA impairs the degradation of NMD target transcripts, establishing CALA as a non-coding regulator of RNA steady-state levels in the endothelium.
