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
Fran Supek, Ben Lehner, Rik G. H. Lindeboom
Summary: The nonsense-mediated mRNA decay (NMD) pathway has been extensively studied to accurately predict the degradation of mRNA with premature termination codons (PTCs). NMD plays a crucial role in disease identification and treatment, as well as in cancer immunotherapy.
TRENDS IN GENETICS
(2021)
Article
Plant Sciences
Miryam A. Cymerman, Helen Saul, Ronit Farhi, Karina Vexler, Dror Gottlieb, Irina Berezin, Orit Shaul
Summary: Translated upstream open reading frames (uORFs) can inhibit the translation of main open reading frames (ORFs) and lead to transcript degradation in eukaryotic cells. In mammalian cells, the length, structure, and reinitiation efficiency of translated uORFs play important roles in determining whether the transcripts will be targeted for degradation by the nonsense-mediated mRNA decay (NMD) pathway. However, the significance of these factors in NMD targeting for plants is still not well-studied.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Editorial Material
Plant Sciences
Yihan Dong, Lyubov A. Ryabova
Summary: In eukaryotes, mRNAs often have uORFs, which can inhibit the translation of the main ORF. In mammals, certain uORFs can trigger mRNA degradation through NMD. However, a study by Cymerman et al. (2023) shows that in Arabidopsis, uORFs with long and structured sequences do not induce mRNA degradation via NMD, in contrast to observations in mammals.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
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
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.
Article
Biochemistry & Molecular Biology
Xiang Meng, Alan Reed, Sandie Lai, Juraj Szavits-Nossan, John E. G. McCarthy
Summary: Gene expression stochasticity is an inherent feature of biological systems, creating non-genetic cellular variation and influencing various processes. In this study, the researchers discovered a distinct form of non-transcriptional noise associated with the translation machinery and mRNA 5'UTR of the GCN4 gene in yeast. They characterized the heterogeneity of translation initiation mediated by GCN4-5'UTR using different techniques and found a subpopulation of cells that consistently exhibited enhanced GCN4 translation under non-starvation conditions.
NUCLEIC ACIDS RESEARCH
(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
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
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.
Article
Multidisciplinary Sciences
Volker Boehm, Sabrina Kueckelmann, Jennifer Gerbracht, Sebastian Kallabis, Thiago Britto-Borges, Janine Altmueller, Marcus Krueger, Christoph Dieterich, Niels H. Gehring
Summary: The degradation of nonsense-mediated mRNA decay (NMD) substrates involves two independent pathways, SMG6-mediated endonucleolytic cleavage and/or SMG5-SMG7-induced accelerated deadenylation. SMG5-SMG7 maintain NMD activity by enabling SMG6 activation. The loss of SMG5-SMG7-dependent pathway can also inactivate the SMG6-dependent branch, indicating a functional connection between the final NMD steps.
NATURE COMMUNICATIONS
(2021)
Article
Medical Laboratory Technology
David N. Louis, Pieter Wesseling, Sebastian Brandner, Daniel J. Brat, David W. Ellison, Felice Giangaspero, Eyas M. Hattab, Cynthia Hawkins, Meagan J. Judge, Bette Kleinschmidt-DeMasters, Takashi Komori, Catriona McLean, Werner Paulus, Arie Perry, Guido Reifenberger, Michael Weller, Brian Rous
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
(2020)
Article
Multidisciplinary Sciences
Sophie A. Dusoswa, Jan Verhoeff, Erik Abels, Santiago P. Mendez-Huergo, Diego O. Croci, Lisan H. Kuijper, Elena de Miguel, Valerie M. C. J. Wouters, Myron G. Best, Ernesto Rodriguez, Lenneke A. M. Cornelissen, Sandra J. van Vliet, Pieter Wesseling, Xandra O. Breakefield, David P. Noske, Thomas Wurdinger, Marike L. D. Broekman, Gabriel A. Rabinovich, Yvette van Kooyk, Juan J. Garcia-Vallejo
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Hematology
Francesco Saettini, Cecilia Poli, Jaime Vengoechea, Sonia Bonanomi, Julio C. Orellana, Grazia Fazio, Fred H. Rodriguez, Loreani P. Noguera, Claire Booth, Valentina Jarur-Chamy, Marissa Shams, Maria Iascone, Maja Vukic, Serena Gasperini, Manuel Quadri, Amairelys Barroeta Seijas, Elizabeth Rivers, Mario Mauri, Raffaele Badolato, Giovanni Cazzaniga, Cristina Bugarin, Giuseppe Gaipa, Wilma G. M. Kroes, Daniele Moratto, Monique M. van Ostaijen-ten Dam, Frank Baas, Silvere van der Maarel, Rocco Piazza, Zeynep H. Coban-Akdemir, James R. Lupski, Bo Yuan, Ivan K. Chinn, Lucia Daxinger, Andrea Biondi
Summary: Agammaglobulinemia, recurrent infections, hypertrophic cardiomyopathy and neutropenia were found in three novel patients in this study. Variants in the gene for folliculin interacting protein 1 (FNIP1) were identified, leading to impaired B-cell metabolism and development. This study highlights the importance of FNIP1 in B-cell development and metabolism.
Article
Surgery
Fons F. van den Berg, Yama Issa, Jeroen P. Vreijling, Markus M. Lerch, Frank Ulrich Weiss, Marc G. Besselink, Frank Baas, Marja A. Boermeester, Hjalmar C. van Santvoort
Summary: Genomic sequencing revealed that ZNF106 and SLC52A1 may be associated with the development of early multiple organ failure in acute pancreatitis.
Article
Clinical Neurology
Krista Kuitwaard, Pieter A. van Doorn, Thiziri Bengrine, Wouter van Rijs, Frank Baas, Sietse Q. Nagelkerke, Taco W. Kuijpers, Willem-Jan R. Fokkink, Carina Bunschoten, Merel C. Broers, Sten P. Willemsen, Bart C. Jacobs, Ruth Huizinga
Summary: Variations in PRF1 and the promoter region of FCGR2B are associated with the response to IVIg in CIDP. These findings, which require validation, are a first step towards the understanding of the heterogeneity in the treatment response in CIDP.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Neurosciences
Ramita Dewan, Ruth Chia, Jinhui Ding, Richard A. Hickman, Thor D. Stein, Yevgeniya Abramzon, Sarah Ahmed, Marya S. Sabir, Makayla K. Portley, Arianna Tucci, Kristina Ibanez, F. N. U. Shankaracharya, Pamela Keagle, Giacomina Rossi, Paola Caroppo, Fabrizio Tagliavini, Maria L. Waldo, Per M. Johansson, Christer F. Nilsson, James B. Rowe, Luisa Benussi, Giuliano Binetti, Roberta Ghidoni, Edwin Jabbari, Coralie Viollet, Jonathan D. Glass, Andrew B. Singleton, Vincenzo Silani, Owen A. Ross, Mina Ryten, Ali Torkamani, Toshiko Tanaka, Luigi Ferrucci, Susan M. Resnick, Stuart Pickering-Brown, Christopher B. Brady, Neil Kowal, John A. Hardy, Vivianna Van Deerlin, Jean Paul Vonsattel, Matthew B. Harms, Huw R. Morris, Raffaele Ferrari, John E. Landers, Adriano Chio, J. Raphael Gibbs, Clifton L. Dalgard, Sonja W. Scholz, Bryan J. Traynor
Summary: Researchers analyzed whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 LBD patients, and 3,158 neurologically healthy subjects, identifying pathogenic HTT gene expansions in a small percentage of FTD/ALS patients but not in the LBD or healthy groups. Postmortem evaluations supported an etiological relationship between HTT repeat expansions and FTD/ALS syndromes, suggesting the importance of genetic screening for HTT repeat expansions in FTD/ALS patients.
Article
Clinical Neurology
Janel O. Johnson, Ruth Chia, Danny E. Miller, Rachel Li, Ravindran Kumaran, Yevgeniya Abramzon, Nada Alahmady, Alan E. Renton, Simon D. Topp, J. Raphael Gibbs, Mark R. Cookson, Marya S. Sabir, Clifton L. Dalgard, Claire Troakes, Ashley R. Jones, Aleksey Shatunov, Alfredo Iacoangeli, Ahmad Al Khleifat, Nicola Ticozzi, Vincenzo Silani, Cinzia Gellera, Ian P. Blair, Carol Dobson-Stone, John B. Kwok, Emily S. Bonkowski, Robin Palvadeau, Pentti J. Tienari, Karen E. Morrison, Pamela J. Shaw, Ammar Al-Chalabi, Robert H. Brown, Andrea Calvo, Gabriele Mora, Hind Al-Saif, Marc Gotkine, Fawn Leigh, Irene J. Chang, Seth J. Perlman, Ian Glass, Anna Scott, Christopher E. Shaw, A. Nazli Basak, John E. Landers, Adriano Chio, Thomas O. Crawford, Bradley N. Smith, Bryan J. Traynor
Summary: This study identified variants in the SPTLC1 gene associated with juvenile ALS, suggesting that screening for these variants may be important for patients presenting with juvenile ALS.
Review
Physiology
Ahlem Achour, Tamara T. Koopmann, Frank Baas, Cornelis L. Harteveld
Summary: Next-generation sequencing (NGS) has rapidly transitioned from a research setting to a clinical application, becoming the preferred method for detecting disease-causing variants in various genetic diseases. NGS plays an important role in screening and diagnosing hemoglobinopathies, with added value in large-scale screening and complex cases. It is a useful addition to existing methods for diagnosing these disorders.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Samoil Sekulovski, Pascal Devant, Silvia Panizza, Tasos Gogakos, Anda Pitiriciu, Katharina Heitmeier, Ewan Phillip Ramsay, Marie Barth, Carla Schmidt, Thomas Tuschl, Frank Baas, Stefan Weitzer, Javier Martinez, Simon Trowitzsch
Summary: Mutations within subunits of the tRNA splicing endonuclease complex are associated with pontocerebellar hypoplasia, and modulation of TSEN stability may contribute to the disease phenotype.
NATURE COMMUNICATIONS
(2021)
Article
Clinical Neurology
Remco J. Hack, Minne N. Cerfontaine, Gido Gravesteijn, Stephan Tap, Anne Hafkemeijer, Jeroen van der Grond, Marie-Noelle Witjes-Ane, Frank Baas, Julie W. Rutten, Saskia A. J. Lesnik Oberstein
Summary: This study is the first genotype-driven, large prospective CADASIL cohort study, and the results indicate that the NOTCH3 EGFr group is the most important modifier in CADASIL disease. Male sex and hypertension also have a significant impact on clinical outcomes and neuroimaging markers.
Article
Biochemistry & Molecular Biology
Florine Seidel, Robert Kleemann, Wim van Duyvenvoorde, Nikki van Trigt, Nanda Keijzer, Sandra van der Kooij, Cees van Kooten, Lars Verschuren, Aswin Menke, Amanda J. Kiliaan, Johnathan Winter, Timothy R. Hughes, B. Paul Morgan, Frank Baas, Kees Fluiter, Martine C. Morrison
Summary: Complement inhibition with an anti-C5 antibody is not effective in reducing the progression of NASH but is beneficial in established atherosclerosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Oncology
Claudia J. C. Meurs, Joost van Rosmalen, Marian B. E. Menke-Pluijmers, Sabine Siesling, Pieter J. J. Westenend
ANNALS OF SURGICAL ONCOLOGY
(2023)
Letter
Oncology
Erik B. van den Akker, Stavros Makrodimitris, Marc Hulsman, Martijn H. Brugman, Tatjana Nikolic, Ted Bradley, Quinten Waisfisz, Frank Baas, Marja E. Jakobs, Daphne de Jong, P. Eline Slagboom, Frank J. T. Staal, Marcel J. T. Reinders, Henne Holstege
Article
Biochemistry & Molecular Biology
Bart Appelhof, Matias Wagner, Julia Hoefele, Anja Heinze, Timo Roser, Margarete Koch-Hogrebe, Stefan D. Roosendaal, Mohammadreza Dehghani, Mohammad Yahya Vahidi Mehrjardi, Erin Torti, Henry Houlden, Reza Maroofian, Farrah Rajabi, Heinrich Sticht, Frank Baas, Dagmar Wieczorek, Rami Abou Jamra
Summary: This study describes eight children with Pontocerebellar hypoplasia (PCH) from four unrelated families carrying homozygous variants in the MINPP1 gene. These variants result in either a complete absence of MINPP1, impaired protein folding, destabilization of protein structure or reduction in protein stability, leading to the pathogenesis of the disease. This study presents MINPP1 as a novel autosomal recessive gene associated with PCH.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Clinical Neurology
Tessa van Dijk, Peter Barth, Frank Baas, Liesbeth Reneman, Bwee Tien Poll-The
Summary: The study confirmed the progressive nature of caudate nucleus atrophy in PCH1B and PCH2A, while the relative sparing of supratentorial structures in MICPCH cases indicates a different pathomechanism.