Article
Biochemistry & Molecular Biology
Tsuyoshi Morita, Ken'ichiro Hayashi
Summary: This study identified a novel Arp5 mRNA isoform that is targeted by nonsense-mediated mRNA decay (NMD) due to premature termination codons. The switch from the canonical Arp5 isoform to the NMD-targeted isoform occurred during differentiation in mouse skeletal muscle cells, suggesting regulation of Arp5 expression by alternative splicing coupled to NMD (AS-NMD). Higher levels of the NMD-targeted isoform were found in muscle and brain tissues, where ARP5 is less expressed.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(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
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
Genetics & Heredity
Nicole A. Teran, Daniel C. Nachun, Tiffany Eulalio, Nicole M. Ferraro, Craig Smail, Manuel A. Rivas, Stephen B. Montgomery
Summary: Through RNA sequencing, it was found that the efficiency of NMD induced by PTVs can be evaluated using allelic imbalance. A predictive model was established, revealing that variant position, allele frequency, and other factors can predict allelic imbalance, and the NMD effects are highly consistent across different tissues and individuals.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Oncology
Patrick C. O. 'Leary, Huadong Chen, Yagmur U. Doruk, Tess Williamson, Benjamin Polacco, Andrew S. McNeal, Tanushree Shenoy, Nupura Kale, Julia Carnevale, Erica Stevenson, David A. Quigley, Jonathan Chou, Felix Y. Feng, Danielle L. Swaney, Nevan J. Krogan, Minkyu Kim, Morgan E. Diolaiti, Alan Ashworth
Summary: Over one million cases of gastric cancer are diagnosed each year globally. A recent study found defects in the DNA damage response pathway in gastric tumors, creating therapeutic opportunities through synthetic lethal approaches. The study also discovered that ATR inhibitors can be used as targeted agents for gastric cancer and identified NMD proteins as potential biomarkers and therapeutic targets.
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
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
Medicine, Research & Experimental
Sara H. Osum, Eunice I. Oribamise, Stanislas M. A. S. Corbiere, Mandy Taisto, Tyler Jubenville, Alex Coutts, Mark N. Kirstein, James Fisher, Christopher Moertel, Ming Du, David Bedwell, David A. Largaespada, Adrienne L. Watson
Summary: Neurofibromatosis type 1 (NF1) is caused by germline mutations in the tumor-suppressor gene NF1, leading to an increased risk of nervous system tumors. In this study, a minipig model of NF1 carrying a premature termination codon (PTC) was used to investigate the potential of nonsense suppression in restoring expression of the NF1-encoded protein neurofibromin. The results showed that nonsense suppression did not significantly increase neurofibromin in primary NF1-'- Schwann cells, but it reduced phosphorylated ERK.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
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
Plant Sciences
Ping Lu, Daipeng Chen, Zhaomei Qi, Haoming Wang, Yitong Chen, Qinhu Wang, Cong Jiang, Jin-Rong Xu, Huiquan Liu
Summary: This study investigates the landscape and regulation of alternative splicing (AS) and alternative polyadenylation (APA) in Fusarium graminearum, a filamentous fungus. The results reveal that AS and APA play important roles in gene expression regulation, with the majority of AS events affecting coding sequences. Unexpectedly, AS transcripts with premature-termination codons are not degraded. Distal APA sites have strong signals, while proximal APA isoforms are highly expressed in F. graminearum. The study also uncovers the roles of 3'-end processing factors in promoting proximal APA site usage and intron splicing. Furthermore, the study suggests intron inclusion and 3'-untranslated region lengthening as novel mechanisms in regulating aging and dormancy in fungi.
Article
Biotechnology & Applied Microbiology
Bo Sun, Liang Chen
Summary: Through genetical genomics, we elucidate the regulatory mechanism of NMD on individual genes across human tissues. We identify genetic variants that influence NMD regulation, which are often missed in traditional eQTL mapping. NMD regulation plays important roles in the brain and has specific genomic positions for NMD-QTLs.
Review
Plant Sciences
Maria Camila Rodriguez Gallo, R. Glen Uhrig
Summary: This mini-review summarizes the current knowledge of plant-specific protein kinase families involved in alternative splicing (AS) regulation and compares them to their counterparts in animals. The extensive phosphorylation of splicing-related proteins in plants is highlighted, underscoring the importance of investigating the impact of AS on protein and post-translational modifications.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Eichi Watabe, Marina Togo-Ohno, Yuma Ishigami, Shotaro Wani, Keiko Hirota, Mariko Kimura-Asami, Sharmin Hasan, Satomi Takei, Akiyoshi Fukamizu, Yutaka Suzuki, Tsutomu Suzuki, Hidehito Kuroyanagi
Summary: The homeostasis of SAM synthetase in C. elegans is maintained through alternative splicing regulation and m(6)A modification, with splicing regulation achieved through NMD and regulated by U6 snRNA methyltransferase.
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
Plant Sciences
Guiomar Martin
Summary: Retrograde signals from chloroplasts control nuclear transcription and coordinate gene expression involved in chloroplast functioning and seedling development. This study investigates the influence of retrograde signaling on alternative splicing and reveals the molecular and biological functions of this regulation. The results show that alternative splicing mimics transcriptional responses triggered by retrograde signals, and both processes depend on the chloroplast-localized protein GUN1. Additionally, light signals antagonistically control retrograde signaling-regulated splicing isoforms, contributing to the opposite roles these signals play in controlling chloroplast functioning and seedling development.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Neurosciences
Xintian You, Irena Vlatkovic, Ana Babic, Tristan Will, Irina Epstein, Georgi Tushev, Gueney Akbalik, Mantian Wang, Caspar Glock, Claudia Quedenau, Xi Wang, Jingyi Hou, Hongyu Liu, Wei Sun, Sivakumar Sambandan, Tao Chen, Erin M. Schuman, Wei Chen
NATURE NEUROSCIENCE
(2015)
Article
Biochemistry & Molecular Biology
Aleksandra E. Kornienko, Irena Vlatkovic, Juergen Neesen, Denise P. Barlow, Florian M. Pauler
Article
Biochemistry & Molecular Biology
Gueney Akbalik, Kasper Langebeck-Jensen, Georgi Tushev, Sivakumar Sambandan, Jennifer Rinne, Irina Epstein, Ivan Cajigas, Irena Vlatkovic, Erin M. Schuman
Article
Oncology
Anna Rommer, Katarina Steinleitner, Hubert Hackl, Christine Schneckenleithner, Maria Engelmann, Marcel Scheideler, Irena Vlatkovic, Robert Kralovics, Sabine Cerny-Reiterer, Peter Valent, Heinz Sill, Rotraud Wieser
Article
Biotechnology & Applied Microbiology
Iveta Y. Yotova, Irena M. Vlatkovic, Florian M. Pauler, Katarzyna E. Warczok, Peter F. Ambros, Mitsuo Oshimura, Hans-Christian Theussl, Manfred Gessler, Erwin F. Wagner, Denise P. Barlow
Article
Biology
Irina Epstein, Georgi Tushev, Tristan J. Will, Irena Vlatkovic, Ivan J. Cajigas, Erin M. Schuman
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2014)
Article
Multidisciplinary Sciences
Ru Huang, Markus Jaritz, Philipp Guenzl, Irena Vlatkovic, Andreas Sommer, Ido M. Tamir, Hendrik Marks, Thorsten Klampfl, Robert Kralovics, Hendrik G. Stunnenberg, Denise P. Barlow, Florian M. Pauler
Article
Medicine, Research & Experimental
Markus Baiersdoerfer, Gabor Boros, Hiromi Muramatsu, Azita Mahiny, Irena Vlatkovic, Ugur Sahin, Katalin Kariko
MOLECULAR THERAPY-NUCLEIC ACIDS
(2019)
Article
Multidisciplinary Sciences
Xi Wang, Xintian You, Julian D. Langer, Jingyi Hou, Fiona Rupprecht, Irena Vlatkovic, Claudia Quedenau, Georgi Tushev, Irina Epstein, Bernhard Schaefke, Wei Sun, Liang Fang, Guipeng Li, Yuhui Hu, Erin M. Schuman, Wei Chen
NATURE COMMUNICATIONS
(2019)
Review
Biochemistry & Molecular Biology
Irena Vlatkovic
Summary: LNP-mRNA vaccines, with their advantages of fast engineering and efficient manufacturing, have shown potential in combating SARS-CoV-2 virus. However, in protein replacement therapy, it is crucial to avoid immune activation.
Review
Biotechnology & Applied Microbiology
Gabor Tamas Szabo, Azita Josefine Mahiny, Irena Vlatkovic
Summary: Since the discovery of the advantages of mRNA vaccines nearly 30 years ago, significant progress has been made in this field. The development of COVID-19 vaccines using mRNA technology has achieved unprecedented success globally, demonstrating the safety and effectiveness of mRNA vaccines in combating COVID-19 and highlighting their potential for other infectious diseases and medical conditions.
Article
Pharmacology & Pharmacy
Irena Vlatkovic, Janos Ludwig, Gabor Boros, Gabor Tamas Szabo, Julia Reichert, Maximilian Buff, Markus Baiersdoerfer, Jonas Reinholz, Azita Josefine Mahiny, Ugur Sahin, Katalin Kariko
Summary: The presence of cap structure is crucial for the translation and stability of IVT mRNA, which plays an important role in the development of vaccines and therapeutics. This article presents a method for assessing the presence of cap structure in IVT mRNA using ribozyme cleavage assays, allowing for the determination of capping efficiency and serving as a reliable quality control method.