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
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.
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.
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
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.
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)
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
Multidisciplinary Sciences
Hanae Sato, Robert H. Singer
Summary: The author developed a single-cell reporter system to investigate cell-to-cell variability of NMD efficiency. The study revealed a wide range of NMD efficiency in different cells, potentially linked to the expression levels of surveillance factors.
NATURE COMMUNICATIONS
(2021)
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)
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)
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
Oncology
Alexander C. Leeksma, Ingrid A. M. Derks, M. Haidar Kasem, Emine Kilic, Annelies de Klein, Martine J. Jager, Arjan A. van de Loosdrecht, Joop H. Jansen, Veronika Navrkalova, Laura M. Faber, Nadja Zaborsky, Alexander Egle, Thorsten Zenz, Sarka Pospisilova, Omar Abdel-Wahab, Arnon P. Kater, Eric Eldering
Summary: Recurrent mutations in SF3B1 are linked to various malignancies and may impact biological effects through altered signaling pathways, but show no significant effects on ATM/p53 response, H2AX phosphorylation, and sensitivity to fludarabine in treatment-naive CLL. Cryptic transcripts associated with SF3B1 mutations are degraded via NMD, with increased expression observed after NMD inhibition. Further research may explore the potential benefit of NMD modulatory agents in SF3B1-mutant patients.
FRONTIERS IN ONCOLOGY
(2021)
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
Cell Biology
Justin W. Mabin, Lauren A. Woodward, Robert D. Patton, Zhongxia Yi, Mengxuan Jia, Vicki H. Wysocki, Ralf Bundschuh, Guramrit Singh
Meeting Abstract
Biochemistry & Molecular Biology
Guramrit Singh, Zhongxia Yi
Article
Genetics & Heredity
Pooja Gangras, Thomas L. Gallagher, Michael A. Parthun, Zhongxia Yi, Robert D. Patton, Kiel T. Tietz, Natalie C. Deans, Ralf Bundschuh, Sharon L. Amacher, Guramrit Singh
Article
Biochemistry & Molecular Biology
Zhongxia Yi, Rene M. Arvola, Sean Myers, Corinne N. Dilsavor, Rabab Abu Alhasan, Bayley N. Carter, Robert D. Patton, Ralf Bundschuh, Guramrit Singh
Summary: This study reveals that nonsense-mediated mRNA decay (NMD) in human cell lines can be dependent on UPF3B or independent of it. UPF3A only weakly activates NMD in wild-type cells, but strongly activates NMD in cells lacking UPF3B.
