Review
Biochemistry & Molecular Biology
Evangelos D. Karousis, Oliver Muehlemann
Summary: The article reviews the important role of NMD in mRNA degradation, discusses its impact on various diseases, and proposes strategies to modulate NMD as potential therapeutic approaches.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
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.
Article
Multidisciplinary Sciences
Edward J. Sanderlin, Melissa M. Keenan, Martin Mense, Alexey S. Revenko, Brett P. Monia, Shuling Guo, Lulu Huang
Summary: This study reveals that CFTR mRNAs with nonsense codons are predominantly degraded by the SMG6-mediated branch of the NMD pathway. This finding provides potential strategies for the treatment of cystic fibrosis.
NATURE COMMUNICATIONS
(2022)
Article
Developmental Biology
Jennifer N. Chousal, Abhishek Sohni, Kristoffer Vitting-Seerup, Kyucheol Cho, Matthew Kim, Kun Tan, Bo Porse, Miles F. Wilkinson, Heidi Cook-Andersen
Summary: Nonsense-mediated RNA decay (NMD) is a highly conserved RNA turnover pathway. In mouse blastocysts, the core NMD factor UPF2 is required for expansion of epiblast cells, indicating the essential role of NMD in embryonic cell proliferation and survival.
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
Bosen You, Yin Sun, Jie Luo, Keliang Wang, Qing Liu, Ruizhe Fang, Bingmei Liu, Fuju Chou, Ronghao Wang, Jialin Meng, Chi-Ping Huang, Shuyuan Yeh, Chawnshang Chang, Wanhai Xu
Summary: The study suggests that androgen receptor (AR) promotes vasculogenic mimicry (VM) formation in ccRCC cells by regulating lncRNA-TANAR/TWIST1 signals, potentially impacting metastasis. This discovery provides a clue for the development of a novel anti-angiogenesis therapy to better suppress ccRCC progression.
Article
Biochemistry & Molecular Biology
Hana Cho, Elizabeth T. Abshire, Maximilian W. Popp, Christoph Proschel, Joshua L. Schwartz, Gene W. Yeo, Lynne E. Maquat
Summary: This study identifies 13 proteins constituting the AKT signaling pathway as novel effectors of nonsense-mediated mRNA decay (NMD). The study shows that AKT supersedes UPF2 in exon-junction complexes (EJCs) and increases UPF1 helicase activity through phosphorylation, contributing to the hyperactivation of NMD in Fragile X syndrome.
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
Cell Biology
Rakesh Sarkar, Shreya Banerjee, Arpita Mukherjee, Mamta Chawla-Sarkar
Summary: The research found that during rotavirus infection, the virus can inhibit the NMD pathway to facilitate its unrestricted replication within host cells, with UPF1 playing an antiviral role in this process.
CELLULAR SIGNALLING
(2022)
Article
Cell Biology
Benjamin L. Zaepfel, Zhe Zhang, Kirstin Maulding, Alyssa N. Coyne, Weiwei Cheng, Lindsey R. Hayes, Thomas E. Lloyd, Shuying Sun, Jeffrey D. Rothstein
Summary: The study found that overexpression of UPF1 protein can mitigate neurotoxicity in C9orf72 ALS/FTD models by reducing the severity of known neurodegenerative phenotypes without affecting NMD function itself.
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
Biology
Yukio Kurihara, Yuko Makita, Masaharu Kawauchi, Ami Kageyama, Tomoko Kuriyama, Minami Matsui
Summary: Recent evidence suggests the existence of readthrough transcripts (RTs), including polycistronic mRNAs, in eukaryotes. This study identifies 271 loci producing polycistronic RTs in Arabidopsis. The accumulation of RTs is increased in NMD-deficient mutants compared to the wild type. Additionally, the translation of the second open reading frames (ORFs) of bicistronic mRNAs is rare. Intergenic splicing (IS) events occur in 158 RTs, and inhibiting splicing promotes the accumulation of RTs.
COMMUNICATIONS BIOLOGY
(2022)
Review
Cell Biology
Jacek Staszewski, Natalia Lazarewicz, Julia Konczak, Iwona Migdal, Ewa Maciaszczyk-Dziubinska
Summary: UPF1 plays a crucial role in mRNA decay pathways and protein quality control. It degrades premature termination codon (PTC)-containing products and can independently degrade target proteins. UPF1 protects cells against the accumulation of misfolded proteins.
Article
Virology
Kazumi Nakano, Nobuaki Karasawa, Masaaki Hashizume, Yuetsu Tanaka, Takeo Ohsugi, Kaoru Uchimaru, Toshiki Watanabe
Summary: Studies have shown that the Rex protein of HTLV-1 suppresses the nonsense-mediated mRNA decay (NMD) pathway by binding to host key regulator Upf1 and interacting with SMG5 and SMG7. It also selectively binds to Upf3B, replacing it with a less active form to reduce NMD activity.
Article
Biochemistry & Molecular Biology
Jianran Hu, Ping Li, Baozhong Shi, Jun Tie
Summary: Imp beta 1 plays a crucial role in NMD by interacting with UPF1 to regulate a wide range of target transcripts, affecting the interaction between UPF1 and other core factors, as well as their nuclear distribution.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Shringar Rao, Alessandro Cinti, Abdelkrim Temzi, Raquel Amorim, Ji Chang You, Andrew J. Mouland
Article
Virology
Shringar Rao, Raquel Amorim, Meijuan Niu, Yann Breton, Michel J. Tremblay, Andrew J. Mouland
Article
Biochemistry & Molecular Biology
Shringar Rao, Sami Hassine, Anne Monette, Raquel Amorim, Luc Desgroseillers, Andrew J. Mouland
Article
Cell Biology
Anne Monette, Meijuan Niu, Lois Chen, Shringar Rao, Robert James Gorelick, Andrew John Mouland
Article
Virology
Cynthia Lungu, Francesco A. Procopio, Ronald J. Overmars, Rob J. J. Beerkens, Jolanda J. C. Voermans, Shringar Rao, Henrieke A. B. Prins, Casper Rokx, Giuseppe Pantaleo, David A. M. C. van de Vijver, Tokameh Mahmoudi, Charles A. B. Boucher, Rob A. Gruters, Jeroen J. A. van Kampen
Article
Oncology
Shringar Rao, Tanvir Hossain, Tokameh Mahmoudi
Summary: Hepatitis B Virus (HBV) infection is a major cause of chronic liver cirrhosis and hepatocellular carcinoma (HCC) worldwide, and organoid technology has emerged as a powerful tool for studying this disease.
Article
Multidisciplinary Sciences
Shringar Rao, Cynthia Lungu, Raquel Crespo, Thijs H. Steijaert, Alicja Gorska, Robert-Jan Palstra, Henrieke A. B. Prins, Wilfred van Ijcken, Yvonne M. Mueller, Jeroen J. A. van Kampen, Annelies Verbon, Peter D. Katsikis, Charles A. B. Boucher, Casper Rokx, Rob A. Gruters, Tokameh Mahmoudi
Summary: This study demonstrates the selective induction of cell death in latent HIV-1-infected cells by DDX3 inhibitors, and provides evidence for the reduction of the inducible HIV-1 reservoir in CD4+ T cells from PLWHIV. The pharmacological targeting of DDX3 shows promise in reversing HIV-1 latency and eliminating the latent reservoir.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Michelle P. Clark, Thao Huynh, Shringar Rao, Liana Mackiewicz, Hugh Mason, Shahla Romal, Michael D. Stutz, Sang H. Ahn, Linda Earnest, Vitina Sozzi, Margaret Littlejohn, Bang M. Tran, Norbert Wiedemann, Elizabeth Vincan, Joseph Torresi, Hans J. Netter, Tokameh Mahmoudi, Peter Revill, Marc Pellegrini, Gregor Ebert
Summary: This study demonstrated a clinically viable strategy for potentially eliminating chronic HBV reservoirs in patients by using orally administered drugs that antagonize the function of cellular inhibitor of apoptosis proteins. The research established a reservoir similar to cccDNA in immunocompetent mice using linearized single genome length HBV DNA and confirmed the clinical relevance of the results using primary human liver organoid models.
CELL DEATH & DISEASE
(2021)