Review
Biochemistry & Molecular Biology
Patricia Martins-Dias, Luisa Romao
Summary: Nonsense mutations can lead to dysfunctional proteins, but nonsense suppression therapy has the potential to restore protein function and treat a variety of genetic disorders. However, the efficiency of suppression may be influenced by nonsense-mediated decay, highlighting the importance of using NMD inhibitors or readthrough-compound potentiators to enhance therapeutic effects.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Virology
Tong-Yun Wang, Guo-Ju Sang, Qian Wang, Chao-Liang Leng, Zhi-Jun Tian, Jin-Mei Peng, Shu-Jie Wang, Ming-Xia Sun, Fan-Dan Meng, Hao Zheng, Xue-Hui Cai, Yan-Dong Tang
Summary: This study attempted to develop a live but replication-incompetent Pseudorabies virus (PRV) using genetic code expansion (GCE) technology. Although the premature termination codon (PTC) harboring PRV was successfully rescued, the incorporation efficacy of unnatural amino acids (UAA) was found to be extremely low. Moreover, the establishment of a stable transgenic cell line for PTC virus replication failed, with orthogonal tRNA(Pyl) identified as a limiting factor.
Review
Biochemistry & Molecular Biology
Roland N. Wagner, Michael Wiessner, Andreas Friedrich, Johanna Zandanell, Hannelore Breitenbach-Koller, Johann W. Bauer
Summary: This review summarizes the current understanding of translation termination and highlights newly discovered pathways that influence its fidelity. It also describes the mechanisms involved in the recognition and readthrough of premature termination codons (PTCs) and reports on compounds that induce PTC readthrough. The ongoing attempts of personalized nonsense suppression therapy in different disease contexts are also reviewed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Laure Bidou, Olivier Bugaud, Goulven Merer, Matthieu Coupet, Isabelle Hatin, Egor Chirkin, Sabrina Karri, Stephane Demais, Pauline Francois, Jean-Christophe Cintrat, Olivier Namy
Summary: In this study, a new drug was developed and evaluated for its clinical potential in treating genetic diseases caused by premature termination codons (PTCs). The drug, TLN468, was found to be more effective than the currently used gentamicin and acted on a broader range of sequences without affecting normal stop codon readthrough.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Gastroenterology & Hepatology
Rachida Amzal, Alice Thebaut, Martine Lapalus, Marion Almes, Brigitte Grosse, Elodie Mareux, Mauricette Collado-Hilly, Anne Davit-Spraul, Laure Bidou, Olivier Namy, Emmanuel Jacquemin, Emmanuel Gonzales
Summary: The study investigated the ability of drugs to induce readthrough of nonsense mutations in ABCB11 in patients with PFIC2. Gentamicin was found to effectively induce readthrough and lead to the expression of full-length proteins in different cell lines, showing potential for readthrough therapy in selected patients with PFIC2.
Article
Biochemistry & Molecular Biology
Jordan M. Mattheisen, Jaina S. Wollowitz, Thomas Huber, Thomas P. Sakmar
Summary: We developed a luciferase-based reporter assay for site-specific bioorthogonal labeling of expressed G protein-coupled receptors (GPCRs) in live cells. The assay compared amber codon suppression efficiency, receptor functionality, and efficiency of different bioorthogonal labeling chemistries. We used three different noncanonical amino acids to incorporate into a GPCR, resulting in successful labeling and functional assessment of the engineered mutants in live cells.
Article
Medicine, Research & Experimental
Federica Corrao, Maria Grazia Zizzo, Marco Tutone, Raffaella Melfi, Ignazio Fiduccia, Pietro Salvatore Carollo, Aldo Di Leonardo, Gaetano Caldara, Riccardo Perriera, Andrea Pace, Beatrice Belmonte, Selene Sammataro, Ivana Pibiri, Laura Lentini
Summary: This study investigated the acute toxicological effects of three Translational Readthrough Inducing Drugs (TRIDs) on mice and found that these drugs showed good tolerability without causing significant adverse effects in the mice.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Geriatrics & Gerontology
Liene Bossaerts, Elisabeth Hens, Bernard Hanseeuw, Rik Vandenberghe, Patrick Cras, Peter P. De Deyn, Sebastiaan Engelborghs, Christine Van Broeckhoven
Summary: The ABCA7 gene mutations, especially PTC mutations, are common in Belgian AD patients. They are enriched in LOAD and EOAD patients, and may be associated with a positive family history of disease.
NEUROBIOLOGY OF AGING
(2021)
Article
Genetics & Heredity
Kuba Nowak, Pawel Blazej, Malgorzata Wnetrzak, Dorota Mackiewicz, Pawel Mackiewicz
Summary: Reprogramming the standard genetic code to incorporate non-canonical amino acids offers new possibilities for medicine, industry, and biotechnology. Various methods of code engineering are available to store new genetic information and produce proteins with novel properties. The study provides a theoretical background for optimal genetic code expansion, discussing the robustness of the new coding system and the analysis of optimal codon sets using graph theory.
Review
Biochemistry & Molecular Biology
Shan Li, Juan Li, Wenjing Shi, Ziyan Nie, Shasha Zhang, Fengdie Ma, Jun Hu, Jianjun Chen, Peiqiang Li, Xiaodong Xie
Summary: This review summarizes the pharmacodynamics and clinical application potential of the main translational readthrough-inducing drugs (TRIDs) discovered so far, especially some newly discovered TRIDs in the past decade. The discovery of these TRIDs brings hope for treating nonsense mutations in various genetic diseases. Further research is still needed to deeply understand the mechanism of eukaryotic cell termination and drug-induced PTC readthrough so that patients can achieve the greatest benefit from the various TRID treatments.
Article
Biology
Erika Alden DeBenedictis, Dieter Soll, Kevin M. Esvelt
Summary: This study investigates the tolerance of the Escherichia coli genetic code to tRNA mutations and found that while most tRNAs can be converted to a quadruplet form, only nine aminoacyl tRNA synthetases can tolerate quadruplet anticodons. This limits the chemical alphabet available for an all-quadruplet code.
Article
Pharmacology & Pharmacy
Renata B. V. Abreu, Thiago T. Gomes, Thales C. Nepomuceno, Xueli Li, Mateus Fuchshuber-Moraes, Giuliana De Gregoriis, Guilherme Suarez-Kurtz, Alvaro N. A. Monteiro, Marcelo A. Carvalho
Summary: This study evaluates the readthrough of clinically relevant PTC variants in the breast and ovarian cancer-predisposing gene BRCA1 for the first time, demonstrating that the aminoglycoside G418 can induce PTC readthrough and restore full-length protein synthesis and function.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biology
Martine Palma, Fabrice Lejeune
Summary: Recognition of the stop codon is crucial for terminating translation and synthesizing the correct size protein. Stop codon readthrough can occur under specific conditions, leading to different protein isoforms, and has potential therapeutic implications for genetic diseases caused by nonsense mutations.
BIOLOGICAL REVIEWS
(2021)
Article
Chemistry, Medicinal
Nesrine Benslimane, Federica Miressi, Camille Loret, Laurence Richard, Angelique Nizou, Ioanna Pyromali, Pierre-Antoine Faye, Frederic Favreau, Fabrice Lejeune, Anne-Sophie Lia
Summary: Nonsense mutations play a role in peripheral neuropathies by causing premature termination codons at the mRNA level. Readthrough molecules or NMD inhibitors, such as amlexanox, could be potential therapies for hereditary neuropathies. In the study, treatment with amlexanox on patient-derived neuronal cells carrying a specific mutation resulted in stabilization of GDAP1 mRNAs and restoration of mitochondrial morphology, highlighting the potential of readthrough molecules and NMD inhibitors for the treatment of genetic alterations in peripheral neuropathies.
Article
Endocrinology & Metabolism
Fei Huang, Jun Zeng, Dan Liu, Jing Zhang, Boluo Liang, Jingping Gao, Rong Yan, Xiaobo Shi, Jianlin Chen, Wanjuan Song, Hua-Lin Huang
Summary: This study identified a novel homozygous frameshift mutation in DNAH6 gene in two patients with asthenoteratozoospermia from a consanguineous Uighur family in China. The mutation led to multiple morphological and ultrastructural abnormalities of spermatozoa. The findings of this study expand the spectrum of genetic mutations associated with asthenoteratozoospermia and may have implications for genetic counseling and assisted reproduction in male infertility.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Virology
Yingtong Feng, Xuyang Guo, Hong Tian, Yuan He, Yang Li, Xuelian Jiang, Haixue Zheng, Shuqi Xiao
Summary: This study identifies a novel transcription factor, HOXA3, which promotes PRRSV replication by negatively regulating HO-1 gene transcription and suppressing the IFN-I response. The study extends the understanding of the function of HOXA3 and provides new insights into the immune evasion mechanism of PRRSV.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Huanan Liu, Kangli Li, Wenzhe Chen, Fan Yang, Weijun Cao, Keshan Zhang, Pengfei Li, Lijie Tang, Zixiang Zhu, Haixue Zheng
Summary: This study reveals a novel mechanism of SVA 2B protein in antagonizing host innate immune response in both human and porcine cells, providing important insights for understanding the pathogenesis of SVA and oncolytic virotherapy.
MOLECULAR IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Hui Liang, Dong-Sheng Ji, Guo-Qiang Xu, Yong-Chun Luo, Haixue Zheng, Peng-Fei Xu
Summary: This study developed a visible-light driven chiral phosphoric acid catalyzed asymmetric reaction, which can synthesize chiral compounds, and it is the first example of constructing a chiral C-O bond using simple alcohols.
Article
Microbiology
Keshan Zhang, Bo Yang, Chaochao Shen, Ting Zhang, Yu Hao, Dajun Zhang, Huanan Liu, Xijuan Shi, Guoli Li, Jinke Yang, Dan Li, Zixiang Zhu, Hong Tian, Fan Yang, Yi Ru, Wei Jun Cao, Jianhong Guo, Jijun He, Haixue Zheng, Xiangtao Liu
Summary: This study identified the function of MGF360-9L protein during ASFV infection. MGF360-9L inhibits IFN-beta signaling through the degradation of STAT1 and STAT2 and is an important virulence gene of ASFV. These findings may guide the development of live attenuated ASFV vaccines.
Article
Microbiology
Yueyue Duan, Liyan Cao, Cong Yuan, Xuepeng Suo, Xiangyu Kong, Yulong Gao, Xiangtong Li, Haixue Zheng, Xiaomei Wang, Qi Wang
Summary: p53 plays a critical role in inhibiting ALV replication by recruiting the HDAC1/2 complex to the ALV promoter. The acetylation status of ALV-bound histones H3 and H4 correlates with ALV viremia in infected chickens.
Article
Immunology
Guowei Xu, Xijuan Shi, Huanan Liu, Chaochao Shen, Bo Yang, Ting Zhang, Xuehui Chen, Dengshuai Zhao, Jinke Yang, Yu Hao, Huimei Cui, Xingguo Yuan, Xiangtao Liu, Keshan Zhang, Haixue Zheng
Summary: African swine fever (ASF) has had a significant impact on pig production in China and the world. Research has found that extracellular vesicles play a critical role in the spread of pathogenic microorganisms and can cause protein differences after infection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Virology
Yueyue Duan, Cong Yuan, Xuepeng Suo, Liyan Cao, Xiangyu Kong, Xiangtong Li, Haixue Zheng, Qi Wang
Summary: This study discovered that pretreatment with Type I interferon (IFN-I) can effectively block the entry of swine acute diarrhea syndrome coronavirus (SADS-CoV) into cells. The inhibition of SADS-CoV entry and replication mediated by IFN-I is significantly impaired in the absence of TET2. This finding suggests that TET2 serves as a checkpoint for IFN-I-mediated inhibition on the cell entry of SADS-CoV, providing a potential therapeutic target for combating SADS-CoV.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Virology
Lingxia Li, Wenping Yang, Xiaoxia Ma, Jinyan Wu, Xiaodong Qin, Xiaoan Cao, Jianhua Zhou, Li Jin, Jijun He, Haixue Zheng, Xiangtao Liu, Dan Li, Youjun Shang
Summary: This study reveals the mechanism by which Peste des petits ruminants virus (PPRV) induces inflammatory responses by regulating the NF-kappa B signaling pathway and NLRP3 inflammasome. PPRV N protein acts as an important proinflammatory factor by directly binding to MyD88 and NLRP3 to promote the assembly and function of the signaling pathway and inflammasome. These findings have important implications for the prevention and treatment of PPRV infection.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
XuSheng Ma, KeShan Zhang, ZhiKuan Luo, XiaoFeng Nian, S. K. Mohiuddin Choudhury, ZiXiang Zhu, Rui Song, JingJing Pei, YanLi Huo, YuanYuan Li, Fan Yang, WeiJun Cao, HuiSheng Liu, XiangTao Liu, HaiXue Zheng
Summary: The present study reveals the regulatory roles of annexin-A1 (ANXA1) in RNA virus-induced interferon production and foot-and-mouth disease virus (FMDV) replication. ANXA1 positively regulates IFN-beta production through the TBK1-IRF3 axis and interacts with JAK1 and STAT1 to enhance signal transduction. FMDV 3A protein interacts with ANXA1 to inhibit its ability to promote IFN-beta production and suppress ANXA1-TBK1 complex formation, thereby modulating viral replication.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Zifang Zheng, Xiali Fu, Xue Ling, Huanhuan Sun, Yang Li, Zhiqian Ma, Bingjie Wei, Haixue Zheng, Shuqi Xiao
Summary: In this study, we identified a novel IRF8-miR-10a-SRP14 regulatory pathway against PRRSV infection, providing new insights into virus-host interactions and suggesting potential new antiviral strategies to control PRRSV.
JOURNAL OF VIROLOGY
(2022)
Article
Microbiology
Zhiwei Li, Zhiqian Ma, Linfang Dong, Ting Yang, Yang Li, Dian Jiao, Weiguo Han, Haixue Zheng, Shuqi Xiao
Summary: This study confirms that the S gene is the decisive gene for PEDV adaptability to monkey Vero cells and porcine LLC-PK1 cells. The exchange of S1 and S2 subunits in adaptive strains does not enable PEDV to adapt to cells, and the 803L and 976H residues in the S2 subunit are critical for rCH/SX/2016-S1(HNXP)+S3(HNXP) adaptation to Vero cells. These findings highlight the crucial role of the PEDV S protein in cell tropism and suggest the potential role of coronaviruses S protein in cross-species transmission. Additionally, this study provides unique insights into identifying PEDV functional receptors and developing PEDV and other coronaviruses vaccines.
Article
Veterinary Sciences
Ting Zhang, Bingzhou Lu, Bo Yang, Dajun Zhang, Xijuan Shi, Chaochao Shen, Huimei Cui, Xingguo Yuan, Dengshuai Zhao, Jinke Yang, Yu Hao, Xuehui Chen, Xiangtao Liu, Keshan Zhang, Haixue Zheng
Summary: This study identified and analyzed the composition of vesicular fluid in pigs after FMD infection for the first time. It found that the proteins in the fluid are related to innate immune and inflammation pathways, and the levels of certain cytokines were significantly increased.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Virology
Caina Ma, Shasha Li, Fan Yang, Weijun Cao, Huisheng Liu, Tao Feng, Keshan Zhang, Zixiang Zhu, Xiangtao Liu, Yonghao Hu, Haixue Zheng
Summary: African swine fever (ASF) is a highly pathogenic disease that affects domestic and wild pigs. There is currently no effective vaccine available. This study found that the host factor FoxJ1 plays a role in inhibiting ASFV replication, while ASFV proteins degrade FoxJ1, weakening its antiviral effect. These findings provide insights for the development of antiviral drugs and vaccines against ASFV infection.
Article
Chemistry, Multidisciplinary
Wan-Lei Yu, Zi-Gang Ren, Ke-Xing Ma, Hui-Qing Yang, Jun-Jie Yang, Haixue Zheng, Wangsuo Wu, Peng-Fei Xu
Summary: This study describes a cobaloxime-catalyzed photochemical dehydrogenation strategy for the direct removal of hydrogen atoms from saturated compounds. The reaction shows good yields, selectivity, and synthetic versatility without the need for external photosensitizers, noble metals, or oxidants, making it potentially useful for synthesis.
Article
Virology
Dan Li, Panxue Wu, Huanan Liu, Tao Feng, Wenping Yang, Yi Ru, Pan Li, Xiaolan Qi, Zhengwang Shi, Haixue Zheng
Summary: Deletion of the QP509L and QP383R genes from the highly virulent ASF virus completely attenuates the virus in pigs. However, the deleted virus does not provide protection against infection by the virulent parental virus. Additionally, the deleted virus induces lower levels of immune-related genes and interferon-beta.
JOURNAL OF VIROLOGY
(2022)