Article
Biochemistry & Molecular Biology
Hui Shen, Robert Jordan Ontiveros, Michael C. Owens, Monica Yun Liu, Uday Ghanty, Rahul M. Kohli, Kathy Fange Liu
Summary: The oxidation of 5-methylcytosine in DNA by TET enzymes is crucial for gene regulation, and recent evidence suggests a biological function for TET-mediated m(5)C oxidation in both mRNA and tRNA. Specifically, TET2-mediated oxidation of m(5)C in tRNA promotes translation and influences tRNA methylation. These findings reveal an unexpected role for TET enzymes in regulating multiple aspects of the central dogma.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ze Liu, Justin Wang, Yi Shi, Brian A. Yee, Markus Terrey, Qian Zhang, Jenq-Chang Lee, Kuo- Lin, Andrew H-J Wang, Susan L. Ackerman, Gene W. Yeo, Haissi Cui, Xiang-Lei Yang
Summary: Translational readthrough of UGA stop codons by selenocysteine-specific tRNA enables the synthesis of selenoproteins. In addition, this mechanism can also increase translational readthrough of non-selenocysteine genes to create C-terminally extended isoforms. The recognition of target mRNAs by seryl-tRNA synthetase is dependent on its enzymatic activity and a vertebrate-specific domain. The findings expand our understanding of selenoprotein biosynthesis and suggest a potential avenue for therapeutic targeting of nonsense mutations using endogenous factors.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Christopher P. Lapointe, Rosslyn Grosely, Masaaki Sokabe, Carlos Alvarado, Jinfan Wang, Elizabeth Montabana, Nancy Villa, Byung-Sik Shin, Thomas E. Dever, Christopher S. Fraser, Israel S. Fernandez, Joseph D. Puglisi
Summary: The study investigates the binding mechanism of human ribosomal subunits using single-molecule spectroscopy and structural methods, revealing the roles and molecular choreography of eukaryotic initiation factors eIF1A and eIF5B during translation initiation in humans.
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
Biochemistry & Molecular Biology
Qi-Yu Zeng, Fan Zhang, Jian-Hui Zhang, Zhoufei Hei, Zi-Han Li, Meng-Han Huang, Pengfei Fang, En-Duo Wang, Xiao-Jian Sun, Xiao-Long Zhou
Summary: TARSL2, the only duplicated aaRS gene in vertebrates, does not play a significant role in mRNA translation in vivo but is essential for mouse development. Deletion of Tarsl2 does not affect tRNAThrs abundance or charging levels, indicating a reliance on Tars1. It is also a peripheral member of the multiple tRNA synthetase complex.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Howard Gamper, Yujia Mao, Isao Masuda, Henri McGuigan, Gregor Blaha, Yuhong Wang, Shoujun Xu, Ya-Ming Hou
Summary: By utilizing the high-efficiency +1-frameshifting SufB2 tRNA, it was discovered that there are two explorations of +1 frameshifting in one elongation cycle of protein synthesis, with the majority occurring during translocation from the A site to the P site. This research demonstrates that the ribosome itself plays a critical role in determining changes in the reading frame, providing insights into the mechanistic parallel of +1 frameshifting with -1 frameshifting.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Howard Gamper, Yujia Mao, Isao Masuda, Henri McGuigan, Gregor Blaha, Yuhong Wang, Shoujun Xu, Ya-Ming Hou
Summary: The study investigates the mechanism of +1 frameshifting during translation using the SufB2 tRNA with an extra nucleotide in the anticodon loop. It reveals that +1 frameshifting occurs twice in one elongation cycle, with the majority of the shift happening during translocation from the A site to the P site, and a fraction occurring within the P site upon A site occupancy in the +1 frame. This work suggests that the ribosome itself plays a crucial role in determining the reading frame changes during protein synthesis.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ting Yu, Junyi Jiang, Qianxi Yu, Xin Li, Fuxing Zeng
Summary: Magnesium ions are abundant and crucial in the ribosome, and a decrease in its concentration leads to ribosome dissociation and structural distortion. This study focused on the structural distortion of the 30S subunit under different magnesium concentrations. The decoding center and h17 were found to be significantly distorted, and the requirement for magnesium ions suggests that these conformational changes may be shared across all domains of life due to magnesium deficiency.
Article
Biochemistry & Molecular Biology
Ali Mostafa Anwar, Saif M. Khodary, Eman Ali Ahmed, Aya Osama, Shahd Ezzeldin, Anthony Tanios, Sebaey Mahgoub, Sameh Magdeldin
Summary: The tRNA adaptation index (tAI) is a translation efficiency metric that considers codon-tRNA wobble interaction efficiencies. The initial implementation had flaws due to species-specific variations in gene expression. The species-specific approach (stAI) was developed, but it struggled to find the global optimum. We developed a new approach called genetic tAI (gtAI) using a genetic algorithm to optimize weights and improve the correlation with the codon adaptation index (CAI) and protein abundance prediction.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Olga A. Postnikova, Sheetal Uppal, Weiliang Huang, Maureen A. Kane, Rafael Villasmil, Igor B. Rogozin, Eugenia Poliakov, T. Michael Redmond
Summary: The SARS-CoV-2 Spike glycoprotein has acquired a unique insert sequence that could affect virus spread and infection mechanisms, prompting further investigation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Nicole Kleiber, Nicolas Lemus-Diaz, Carina Stiller, Marleen Heinrichs, Mandy Mong-Quyen Mai, Philipp Hackert, Ricarda Richter-Dennerlein, Claudia Hoebartner, Katherine E. Bohnsack, Markus T. Bohnsack
Summary: RNA modifications, specifically the enzyme METTL8, play a crucial role in regulating RNA functions and have significant impacts on tRNA structure and mitochondrial translation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Amrita Saha, Nilashis Nandi
Summary: Aminoacylation reaction, the first step of protein biosynthesis, relies on aminoacyl tRNA synthetase enzyme for catalysis. In this study, it was found that Mg2+ ions bound to tRNA significantly influence the charging step of the reaction, indicating the necessity of Mg2+ presence for successful aminoacylation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Claire Fergus, Mashael Al-Qasem, Michelle Cotter, Ciara M. McDonnell, Emiliano Sorrentino, Franciane Chevot, Karsten Hokamp, Mathias O. Senge, John M. Southern, Stephen J. Connon, Vincent P. Kelly
Summary: Base modification can occur throughout a transfer RNA molecule, with a particular emphasis on position 34 of the anticodon loop. Human enzymes can recognize a wide range of artificial derivatives for transfer RNA incorporation, while displaying strict specificity for decoding certain codons. Exploiting the queuosine incorporation pathway shows broad potential for intentionally engineering chemical diversity into transfer RNA anticodons.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Simon Hollerer, Markus Jeschek
Summary: Translation is a critical factor in gene expression and biotechnology engineering. Through a systematic assessment of over 1.2 million 5'-UTR-CDS pairs in E. coli, we find that 5'-UTR and CDS individually contribute to 53% and 20% of translation variance, respectively. Our study disproves the hypothesis that tRNA abundance explains expression changes between CDSs with different codons and provides experimental evidence for a base-pairing interaction between initiator tRNA and mRNA. This demonstrates the importance of ultradeep sequence-function mapping in accurately understanding gene regulation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Sabrina M. Huber, Ulrike Begley, Anwesha Sarkar, William Gasperi, Evan T. Davis, Vasudha Surampudi, May Lee, J. Andres Melendez, Peter C. Dedon, Thomas J. Begley
Summary: Cells respond to environmental stress by regulating gene expression at the level of both transcription and translation. The dynamic regulation of transfer RNA (tRNA) wobble modifications leads to selective translation of stress response proteins. This study reveals that the response of human hepatocellular carcinoma cells to arsenite exposure is regulated by the availability of queuine, a precursor to tRNA wobble modification. Limiting queuine leads to cell death, altered translation, increased reactive oxygen species levels, and mitochondrial dysfunction.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Nelli F. Khabibullina, Andrey G. Tereshchenkov, Ekaterina S. Komarova, Egor A. Syroegin, Dmitrii I. Shiriaev, Alena Paleskava, Victor G. Kartsev, Alexey A. Bogdanov, Andrey L. Konevega, Olga A. Dontsova, Petr V. Sergiev, Ilya A. Osterman, Yury S. Polikanov
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2019)
Article
Biochemistry & Molecular Biology
Daria S. Vinogradova, Victor Zegarra, Elena Maksimova, Jose Alberto Nakamoto, Pavel Kasatsky, Alena Paleskava, Andrey L. Konevega, Pohl Milon
Review
Biochemistry & Molecular Biology
Marija Liutkute, Ekaterina Samatova, Marina V. Rodnina
Article
Biochemistry & Molecular Biology
A. Shvetsov, D. Lebedev, Y. A. Zabrodskaya, A. A. Shaldzhyan, M. A. Egorova, D. S. Vinogradova, A. L. Konevega, A. N. Gorshkov, E. S. Ramsay, A. Radulescu, M. Sergeeva, M. A. Plotnikova, A. B. Komissarov, A. S. Taraskin, K. Lebedev, Yu P. Garmay, V. V. Kuznetsov, V. V. Isaev-Ivanov, A. V. Vasin, L. M. Tsybalova, V. V. Egorov
Summary: The study examined the molecular interactions of two influenza A nucleoprotein variants in oligomeric form, showing that the E292G mutation impacts cold adaptation. The distance between nucleoprotein complex strands and the melting temperature of the complexes were affected by the mutations. Additionally, the study revealed differences in structure and flexibility of the complexes at different temperatures, shedding light on the mechanism of cold adaptation associated with the E292G mutation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Oncology
Elena Shramova, Galina Proshkina, Victoria Shipunova, Anastasia Ryabova, Roman Kamyshinsky, Andrey Konevega, Aleksey Schulga, Elena Konovalova, Georgij Telegin, Sergey Deyev
Article
Infectious Diseases
Chih-Wei Chen, Julia A. Pavlova, Dmitrii A. Lukianov, Andrey G. Tereshchenkov, Gennady I. Makarov, Zimfira Z. Khairullina, Vadim N. Tashlitsky, Alena Paleskava, Andrey L. Konevega, Alexey A. Bogdanov, Ilya A. Osterman, Natalia V. Sumbatyan, Yury S. Polikanov
Summary: The semi-synthetic triphenylphosphonium analog of chloramphenicol, CAM-C4-TPP, shows stronger affinity and higher inhibitory potency towards bacterial ribosomes than chloramphenicol. Its X-ray crystal structure reveals the compound's unique binding mode and potential as a chemical scaffold for further development in medicinal chemistry.
Article
Infectious Diseases
Julia A. Pavlova, Zimfira Z. Khairullina, Andrey G. Tereshchenkov, Pavel A. Nazarov, Dmitrii A. Lukianov, Inna A. Volynkina, Dmitry A. Skvortsov, Gennady I. Makarov, Etna Abad, Somay Y. Murayama, Susumu Kajiwara, Alena Paleskava, Andrey L. Konevega, Yuri N. Antonenko, Alex Lyakhovich, Ilya A. Osterman, Alexey A. Bogdanov, Natalia V. Sumbatyan
Summary: This study synthesized and studied new chimeric compounds that combine chloramphenicol and triphenylphosphonium, showing dual action targeting both bacterial ribosomes and cellular membranes. These compounds demonstrated inhibitory effects on CHL-resistant bacterial strains in addition to suppressing protein synthesis.
Article
Biochemistry & Molecular Biology
Alena Paleskava, Elena M. Maksimova, Daria S. Vinogradova, Pavel S. Kasatsky, Stanislav Kirillov, Andrey L. Konevega
Summary: The study found that replacing elongation factors with thermophilic proteins in an in vitro translation system affected the rates of A-site binding and decoding reactions, while translocation kinetics were influenced differently. This suggests the importance of elongation factors in the translation process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jose A. Nakamoto, Wilfredo Evangelista, Daria S. Vinogradova, Andrey L. Konevega, Roberto Spurio, Attilio Fabbretti, Pohl Milon
Summary: Initiation factor IF3 is crucial for accurate and fast bacterial mRNA translation initiation. The interplay between IF3 domains is dynamic and responsive to the binding of 30S ligands. IF1 and IF2 play a role in compacting IF3 structure, while IF3N and IF3C are involved in binding different proteins and tRNAs to ensure accurate translation initiation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
George A. Saratov, Vasiliy I. Vladimirov, Alexey L. Novoselov, Rustam H. Ziganshin, Guo Chen, Timur N. Baymukhametov, Andrey L. Konevega, Alexey A. Belogurov, Anna A. Kudriaeva
Summary: In this study, the researchers characterized human constitutive and immune 20S and 26S/30S proteasomes using engineered versions fused with different subunits. They found that immunoproteasomes produced peptides that can be directly loaded onto HLA class I molecules, based on their hydrolysis of the multiple sclerosis autoantigen MBP. They identified five immunodominant core regions of MBP, and found that all peptides, except one, were associated with HLA I alleles known to increase MS risk. They also observed that certain HLA-A*44 molecules showed high affinity binding to a specific MBP peptide, potentially linking their protective phenotype to the depletion of autoreactive cytotoxic T cells or induction of CD8+ regulatory T cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Madhura N. Paranjpe, Valeria Marina, Aleksandr A. Grachev, Tinashe P. Maviza, Olga A. Tolicheva, Alena Paleskava, Ilya A. Osterman, Petr Sergiev, Andrey L. Konevega, Yury S. Polikanov, Matthieu G. Gagnon
Summary: Thermorubin (THR) is an antibiotic that can inhibit translation initiation and disrupt tRNA accommodation in the ribosomal A site, causing ribosome stalling at internal and termination codons. Our findings reveal that THR affects multiple steps of translation elongation and can coexist with P- and A-site tRNAs, allowing ribosomes to continue elongation in the presence of the drug.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Infectious Diseases
Julia A. Pavlova, Andrey G. Tereshchenkov, Pavel A. Nazarov, Dmitrii A. Lukianov, Dmitry A. Skvortsov, Vladimir I. Polshakov, Byasilya F. Vasilieva, Olga V. Efremenkova, Mikhail Y. Kaiumov, Alena Paleskava, Andrey L. Konevega, Olga A. Dontsova, Ilya A. Osterman, Alexey A. Bogdanov, Natalia V. Sumbatyan
Summary: To improve the properties of antimicrobial compounds, new conjugates were synthesized and studied, which consisted of two different biologically active agents in a single chimeric molecule based on chloramphenicol and a hydrophobic cation. These conjugates, named CAM-Cn-BER, effectively bound to the bacterial ribosome and inhibited protein synthesis, similar to chloramphenicol. CAM-C8-BER displayed selective inhibition of Gram-positive bacteria and acted on both the ribosome and the cell membrane. Moreover, CAM-Cn-BERs did not inhibit eukaryotic translation and were non-toxic to eukaryotic cells.
Article
Biochemistry & Molecular Biology
Evgeniia A. Diatlova, Grigory V. Mechetin, Anna V. Yudkina, Vasily D. Zharkov, Natalia A. Torgasheva, Anton V. Endutkin, Olga V. Shulenina, Andrey L. Konevega, Irina P. Gileva, Sergei N. Shchelkunov, Dmitry O. Zharkov
Summary: The protein encoded by the D4R gene in vaccinia virus has both base excision repair uracil-DNA N-glycosylase (vvUNG) activity and acts as a processivity factor in the viral replication complex. The processivity of vvUNG has been characterized using the correlated cleavage assay, which suggests that it plays a role in lesion search through one-dimensional diffusion. Inhibitors carrying a tetrahydro-2,4,6-trioxopyrimidinylidene moiety can suppress the processivity of vvUNG.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Nhan Hau Tran, Vyacheslav Ryzhov, Andrey Volnitskiy, Dmitry Amerkanov, Fedor Pack, Aleksander M. Golubev, Alexandr Arutyunyan, Anastasiia Spitsyna, Vladimir Burdakov, Dmitry Lebedev, Andrey L. Konevega, Tatiana Shtam, Yaroslav Marchenko
Summary: In this study, the potential of iron oxide nanoparticles as radiosensitizers in glioblastoma cells was evaluated. The results showed that the nanoparticles can significantly enhance the effect of X-ray irradiation, while having a weaker or no effect on gamma and proton irradiation. The findings suggest that the nanoparticles may enhance radiation therapy by generating secondary electrons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Biophysics
O. Shulenina, B. F. Yarovoy, S. Kirillov, A. Paleskava, A. L. Konevega
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
(2018)