Article
Biochemistry & Molecular Biology
Fabrice Lejeune
Summary: Nonsense-mediated mRNA decay (NMD) is a mechanism for rapidly eliminating mRNAs with premature termination codons and also regulates multiple genes. Researchers have discovered that NMD must be regulated to express genes that are normally repressed by NMD under specific physiological conditions, so a comprehensive understanding of NMD regulation is important for therapeutic purposes.
Article
Biochemistry & Molecular Biology
Sarah E. Fritz, Soumya Ranganathan, Clara D. Wang, J. Robert Hogg
Summary: This study reveals that an alternative isoform of the core NMD factor UPF1, UPF1(LL), can remodel the specificity of NMD in response to cellular stress. UPF1(LL) is able to bypass specific protective RNA binding proteins, bind and down-regulate transcripts with long 3'UTRs, and induce NMD in response to cellular stress conditions.
Article
Clinical Neurology
Gabrielle Zuniga, Simon Levy, Paulino Ramirez, Jasmine De Mange, Elias Gonzalez, Maria Gamez, Bess Frost
Summary: This study investigates the mechanisms behind altered RNA processing in tauopathies, specifically focusing on the reduction of nonsense-mediated mRNA decay (NMD) activity. The researchers find that deficits in NMD contribute to neurodegeneration in tauopathy through aberrant RNA export and accumulation. They identify a pharmacological activator of NMD that suppresses neurodegeneration in a tau transgenic Drosophila model, suggesting potential therapeutic value for tauopathy patients.
ALZHEIMERS & DEMENTIA
(2023)
Review
Genetics & Heredity
Preeti Nagar, Md Rafikul Islam, Mohammad Alinoor Rahman
Summary: NMD is a mechanism that ensures gene expression accuracy and regulation by degrading erroneous transcripts and modulating the abundance of endogenous mRNAs. It plays diverse biological functions during development, adaptation, and stress response. In tumorigenesis, NMD can be exploited by tumor cells to degrade specific mRNAs or suppressed to promote the expression of oncoproteins.
Article
Biochemistry & Molecular Biology
Damaris Wallmeroth, Jan-Wilm Lackmann, Sabrina Kueckelmann, Janine Altmueller, Christoph Dieterich, Volker Boehm, Niels H. Gehring
Summary: The paralogous proteins UPF3A and UPF3B in humans play important roles in recognizing mRNAs targeted by nonsense-mediated mRNA decay (NMD). UPF3B supports NMD by bridging an exon junction complex (EJC) to the NMD factor UPF2. The role of UPF3A has been described as either a weak NMD activator or an NMD inhibitor. However, knockout or overexpression of UPF3A or knockout of UPF3B did not significantly affect global NMD activity. Co-depletion of UPF3A and UPF3B resulted in NMD inhibition, indicating functional redundancy between these two NMD factors.
Review
Virology
Md Robel Ahmed, Zhiyou Du
Summary: The interaction between viruses and hosts is dynamic and evolutionary. Eukaryotic hosts have multiple defense mechanisms against viral infection, including the nonsense-mediated mRNA decay (NMD) system. NMD ensures the accuracy of mRNA translation by degrading abnormal mRNAs. Many RNA viruses have internal stop codons (iTC), which activate NMD and lead to degradation of viral genomes. Some viruses are sensitive to NMD-mediated antiviral defense, while others have evolved mechanisms to overcome or escape NMD. This review summarizes the current understanding of NMD-mediated viral RNA degradation and the ways in which viruses compromise NMD for better infection.
Article
Biochemistry & Molecular Biology
Julie Carrard, Fiona Ratajczak, Josephine Elsens, Catherine Leroy, Rebekah Kong, Lucie Geoffroy, Arnaud Comte, Guy Fournet, Benoit Joseph, Xiubin Li, Sylvie Moebs-Sanchez, Fabrice Lejeune
Summary: The study has built a new screening system and identified two new molecules that can effectively inhibit nonsense-mediated mRNA decay (NMD). These molecules show no cellular toxicity at tested concentrations and have been validated in a lung cancer model with a nonsense mutation.
Review
Biochemistry & Molecular Biology
Lingling Sun, Justine Mailliot, Christiane Schaffitzel
Summary: Nonsense-mediated mRNA decay (NMD) is a cellular surveillance mechanism that degrades mRNAs with a premature stop codon and downregulates the expression of endogenous transcripts. The core NMD factors are conserved from yeast to human, but mammals have diversified NMD pathways with additional factors. This review summarizes the molecular mechanisms and cellular roles of NMD and discusses its implications in neurodevelopmental diseases, cancer, and strategies used by RNA viruses to evade recognition by the NMD machinery.
Article
Cell Biology
Alison J. Inglis, Alina Guna, Angel Galvez-Merchan, Akshaye Pal, Theodore K. Esantsi, Heather R. Keys, Evgeni M. Frenkel, Robert Oania, Jonathan S. Weissman, Rebecca M. Voorhees
Summary: Translation of mRNAs containing premature termination codons (PTCs) results in truncated protein products with deleterious effects. Nonsense-mediated decay (NMD) is responsible for detecting and degrading these proteins, and it relies on the ubiquitin proteasome pathway. Screening experiments identified factors involved in NMD-associated protein quality control and revealed a shared recognition event for both mRNA and protein branches of NMD.
JOURNAL OF CELL SCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Justine Mailliot, Mirella Vivoli-Vega, Christiane Schaffitzel
Summary: Nonsense-mediated messenger RNA decay (NMD) is an important mRNA degradation pathway in eukaryotic cells, controlling mRNA quality and abundance, as well as degrading viral RNA. NMD recognizes mRNAs with premature termination codons (PTCs) and targets them for degradation through a branched network of interconnected pathways. The structural understanding and functional interplay of mammalian NMD factors, such as UPF1, UPF3B, and UPF3A, play crucial roles in NMD pathway choice and regulation. The context-dependent nature of mammalian NMD, determined by developmental stage, tissue, and cell types, further highlights the complexity of gene regulation in this pathway.
BIOCHEMICAL JOURNAL
(2022)
Article
Cell Biology
Yanjie Tan, Jing Zhang, Yi Jin
Summary: Skeletal muscle regeneration is a vital physiological process that responds to injury or disease. Nonsense-mediated mRNA decay (NMD) has been found to inhibit myoblast differentiation by targeting the phosphoinositide-3-kinase regulatory subunit 5 gene, leading to the suppression of MyoD's transcriptional activity. Inhibiting NMD can accelerate muscle regeneration, making it a potential therapeutic target for muscle-related injuries and diseases.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Cell Biology
Giao Vu Quynh Tran, Jens Kleinehr, Hannah Franziska Preugschas, Darisuren Anhlan, Fakry Fahmy Mohamed, Christina Ehrhardt, Stephan Ludwig, Eike Roman Hrincius
Summary: Research has shown that nonsense-mediated mRNA decay (NMD) has restricting capacities against positive-sense single-stranded RNA viruses but limited impact on negative-sense single-stranded RNA viruses. While knockdown of NMD components slightly increased viral mRNA and protein levels, it did not significantly alter viral replication, suggesting that NMD may not effectively restrict (-)ssRNA viruses.
CELLULAR MICROBIOLOGY
(2021)
Review
Cell Biology
Kristoffer Leon, Melanie Ott
Summary: The Nonsense-mediated mRNA Decay (NMD) pathway is a conserved RNA quality control pathway in eukaryotic cells, playing roles in controlling viral pathogens and maintaining homeostasis.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kyle T. Powers, Flint Stevenson-Jones, Sathish K. N. Yadav, Beate Amthor, Joshua C. Bufton, Ufuk Borucu, Dakang Shen, Jonas P. Becker, Daria Lavysh, Matthias W. Hentze, Andreas E. Kulozik, Gabriele Neu-Yilik, Christiane Schaffitzel
Summary: The study shows that BIaS inhibits translation elongation and termination in mammals by distorting the 3'CCA tail of the P-site tRNA and interfering with the accommodation of eRF1 into the peptidyl transferase center. Additionally, BIaS inhibits nonsense-mediated mRNA decay and modulates translation dynamics at premature termination codons in human cells.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Cell Biology
Paul Jongseo Lee, Suzhou Yang, Yu Sun, Junjie U. Guo
Summary: Eukaryotes have evolved various mRNA surveillance mechanisms, with NMD functioning as a quality control mechanism and posttranscriptional gene regulation.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Daniel L. Kiss, William Baez, Kay Huebner, Ralf Bundschuh, Daniel R. Schoenberg
Article
Biochemistry & Molecular Biology
Jackson B. Trotman, Andrew J. Giltmier, Chandrama Mukherjee, Daniel R. Schoenberg
NUCLEIC ACIDS RESEARCH
(2017)
Article
Biochemistry & Molecular Biology
Jackson B. Trotman, Bernice A. Agana, Andrew J. Giltmier, Vicki H. Wysocki, Daniel R. Schoenberg
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Physiology
Julie A. Dougherty, Naresh Kumar, Mohammad Noor, Mark G. Angelos, Mohsin Khan, Chun-An Chen, Mahmood Khan
FRONTIERS IN PHYSIOLOGY
(2018)
Article
Chemistry, Multidisciplinary
Pala Arunkumar, Julie A. Dougherty, Jessica Weist, Naresh Kumar, Mark G. Angelos, Heather M. Powell, Mahmood Khan
Article
Multidisciplinary Sciences
Naresh Kumar, Julie A. Dougherty, Heather R. Manring, Ibrahim Elmadbouh, Muhamad Mergaye, Andras Czirok, Dona Greta Isai, Andriy E. Belevych, Lianbo Yu, Paul M. L. Janssen, Paolo Fadda, Sandor Gyorke, Maegen A. Ackermann, Mark G. Angelos, Mahmood Khan
SCIENTIFIC REPORTS
(2019)
Article
Biochemistry & Molecular Biology
Daniel del Valle Morales, Jackson B. Trotman, Ralf Bundschuh, Daniel R. Schoenberg
NUCLEIC ACIDS RESEARCH
(2020)
Article
Cell Biology
Brianna D. Guarino, Ravi K. Adapala, Anantha K. Kanugula, Nina M. Lenkey, Julie A. Dougherty, Sailaja Paruchuri, Mahmood Khan, Charles K. Thodeti
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2019)
Article
Cell Biology
Julie A. Dougherty, Nil Patel, Naresh Kumar, Shubha Gururaja Rao, Mark G. Angelos, Harpreet Singh, Chuanxi Cai, Mahmood Khan
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Article
Materials Science, Biomaterials
Divya Sridharan, Arunkumar Palaniappan, Britani N. Blackstone, Julie A. Dougherty, Naresh Kumar, Polani B. Seshagiri, Nazish Sayed, Heather M. Powell, Mahmood Khan
Summary: The study demonstrates that coaxial PCL-gelatin nanofibrous scaffolds can be used as a 3D culture platform for efficient differentiation of hiPSCs to functional cardiomyocytes. While there were no significant differences in the morphology and immunofluorescence staining of cardiomyocytes between 2D and 3D cultures, gene expression data showed increased expression of cardiac progenitor genes in 3D cultures and cardiomyocytes markers in 2D cultures.
MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Naresh Kumar, Divya Sridharan, Arunkumar Palaniappan, Julie A. Dougherty, Andras Czirok, Dona Greta Isai, Muhamad Mergaye, Mark G. Angelos, Heather M. Powell, Mahmood Khan
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2020)
Article
Biotechnology & Applied Microbiology
Brianna Guarino, Venkatesh Katari, Ravi Adapala, Neha Bhavnani, Julie Dougherty, Mahmood Khan, Sailaja Paruchuri, Charles Thodeti
Summary: This study demonstrates that t-EVs induce endothelial cell phenotypic transition and abnormal angiogenesis through post-translational downregulation of TRPV4 and activation of the Rho/Rho kinase/YAP/VEGFR2 pathways. Furthermore, t-EVs can induce abnormal vessel formation in vivo independently of tumors, suggesting their potential as novel targets for vascular normalization and cancer therapy.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Biochemical Research Methods
Divya Sridharan, Nooruddin Pracha, Julie A. Dougherty, Ali Akhtar, Syed Baseeruddin Alvi, Mahmood Khan
Summary: Masson's Trichrome Staining is a useful tool for analyzing fibrosis and identifying collagen fibers in different tissues. This study developed a simple protocol to assess cardiac fibrosis and addressed challenges in the immunostaining process.
METHODS AND PROTOCOLS
(2022)
Article
Biochemistry & Molecular Biology
Bernice A. Agana, Vicki H. Wysocki, Daniel R. Schoenberg
Article
Biochemistry & Molecular Biology
Daniel L. Kiss, Catherine E. Waters, Iman M. Ouda, Joshua C. Saldivar, Jenna R. Karras, Zaynab A. Amin, Seham Mahrous, Teresa Druck, Ralf A. Bundschuh, Daniel R. Schoenberg, Kay Huebner
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2017)