Article
Biochemistry & Molecular Biology
Hitotaka Sato, Akash Chandela, Yoshihito Ueno
Summary: The lack of stability in natural nucleosides hinders their application in siRNA-mediated RNAi. Chemical modifications, such as (S)-5'-C-aminopropyl-2'-fluorouridine (5'-AP-2'-FU), have been developed to improve their stability and pharmacokinetic properties. 5'-AP-2'-FU modification enhances the thermal stability of dsRNAs in a position-specific manner and shows resistance against nuclease degradation.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Daniel Englert, Regina Matveeva, Murat Sunbul, Richard Wombacher, Andres Jaschke
Summary: This study describes the development of a proximity-induced bio-orthogonal inverse electron-demand Diels-Alder reaction for covalent RNA labeling, utilizing the high-affinity interaction between a dienophile-modified RhoBAST aptamer and its tetramethyl rhodamine methyltetrazine substrate.
CHEMICAL COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Magda Lewandowska, Ton Sharoni, Yael Admoni, Reuven Aharoni, Yehu Moran
Summary: The study characterized the antiviral immune response of the cnidarian Nematostella vectensis and showed that its RLR paralogs exhibit features distinctive for both vertebrate and invertebrate systems. The functional evidence provided supports the conserved role of RLRs in initiating immune response to dsRNA before the cnidarian-bilaterian split, laying a foundation for further research on the evolution of immune responses to RNA viruses.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Chemistry, Multidisciplinary
Yali Feng, Jing Fang, Yan Zhao, Shuyue Ye, Anna Wang, Yuqi Zhang, Jinfeng Zhu, Jiachen Li, Zhengzhong Lv, Zhongsheng Zhao, Haibin Shi
Summary: In this study, a near-infrared light-mediated mitochondrial RNA modification approach was developed for long-term imaging and effective tumor suppression. A tumor-targetable NIR fluorescent probe f-CRI was synthesized and it could covalently bind to mtRNA upon 808 nm irradiation, leading to prolonged retention in tumors. The covalent modification of mtRNA by f-CRI disrupted mitochondrial function and significantly suppressed tumor growth. This approach provides a potential strategy for cancer RNA interference therapeutics.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Ryota Yamagami, Jacob P. Sieg, Sarah M. Assmann, Philip C. Bevilacqua
Summary: RNA structure is crucial for cellular events, and the study of tRNA structure is challenging. The tRNA structure-seq workflow accurately determines the in vivo secondary structure of tRNA and provides insights into tRNA abundance and natural modifications.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Dandan Qian, Ye Cong, Runhao Wang, Quan Chen, Chuangye Yan, Deshun Gong
Summary: This study presents the cryo-electron microscopy structures of human SIDT2, which forms a dimer and acts as a transporter rather than a channel. Additionally, it exhibits ceramidase activity. These findings enhance our understanding of the structure-function relationships in the SID1 family proteins.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Melissa van Duelmen, Nils Muthmann, Andrea Rentmeister
Summary: Eukaryotic mRNAs can be modified with site-specific chemo-enzymatic methods to enhance immune response, offering a potential strategy for future therapeutic applications.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Jiri Frantisek Potuznik, Ondrej Nesuta, Anton Skriba, Barbora Volenikova, Maria-Bianca Mititelu, Flaminia Mancini, Valentina Serianni, Henri Fernandez, Kristina Spustova, Jana Trylcova, Pavel Vopalensky, Hana Cahova
Summary: The expansion of RNA chemical modifications has revealed new aspects of gene regulation. We discovered a new non-canonical RNA cap, Ap(4)A, which is abundant in human and rat cell lines. Our study showed that Ap(4)A-RNA is recognized as self by the cell and does not elicit an immune response.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Jungang Zhou, Lin Qiu, Qiyao Liang, Yi Zhou, Jinjun Sun, Qiao Gao, Hualiang He, Wenbing Ding, Jin Xue, Youzhi Li
Summary: Chilo suppressalis is a destructive rice pest in China, and the excessive use of insecticides has led to pesticide resistance. The novel pesticide cyproflanilide has high efficacy against C. suppressalis but its toxicity and detoxification mechanisms are not clear. We conducted bioassay experiments and field trials, finding that cyproflanilide was highly toxic to C. suppressalis and had a 91.24% control efficiency. Transcriptome analysis revealed that certain genes (CYP4G90 and CYP4AU10) were up-regulated in response to cyproflanilide exposure, and silencing these genes increased mortality. These findings provide insights into the toxicological basis of cyproflanilide and offer potential for developing resistance management tools for C. suppressalis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Meng Liu, Gangqiang Guo, Pengge Qian, Jianbing Mu, Binbin Lu, Xiaoqin He, Yanting Fan, Xiaomin Shang, Guang Yang, Shijun Shen, Wenju Liu, Liping Wang, Liang Gu, Quankai Mu, Xinyu Yu, Yuemeng Zhao, Richard Culleton, Jun Cao, Lubin Jiang, Thomas E. Wellems, Jing Yuan, Cizhong Jiang, Qingfeng Zhang
Summary: m5C modification is an important regulator of mRNA stability and translation efficiency in malaria parasites. This study characterized the landscape of m5C mRNA modifications in different developmental stages of rodent and human malaria parasites. The results showed that m5C modifications confer stability to Plasmodium transcripts and that NSUN2 is a major mRNA m5C methyltransferase in malaria parasites. Knockout of the nsun2 gene resulted in reduced m5C modification and impaired gametocyte production, which was rescued by restoration of the nsun2 gene. These findings highlight the significant role of NSUN2-mediated m5C modifications in mRNA transcript stability and sexual differentiation in malaria parasites.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Engineering, Environmental
Nazanin Mokhtari, Mohammad Dinari, Hossein Fashandi
Summary: The shortage of water resources and the increased demand for clean water have led to focused investigations on wastewater treatment. Mixed matrix membranes (MMMs) have been introduced as economic and efficient tools for removing contaminants from wastewater. This study synthesized a hydrazone-linked covalent organic framework (Hz-TFPTZ-COF) and incorporated it into a polysulfone (PSf)/poly N-vinylpyrrolidone (PVP) matrix to obtain MMMs with different concentrations of Hz-TFPTZ-COF. The results showed that even at a low concentration of 1.0 wt%, the MMMs exhibited superior performance in terms of pure water permeability and dye rejection.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Chemistry, Medicinal
Francesca Ferlenghi, Laura Scalvini, Federica Vacondio, Riccardo Castelli, Nicole Bozza, Giuseppe Marseglia, Silvia Rivara, Alessio Lodola, Silvia La Monica, Roberta Minari, Pier Giorgio Petronini, Roberta Alfieri, Marcello Tiseo, Marco Mor
Summary: A new compound 11 was developed as a potent and irreversible inhibitor of EGFR(L858R/T790M/C797S), showing higher activity than osimertinib. However, it did not inhibit the triple mutant EGFR(del19/T790M/C797S).
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Na Zhang, Junquan Lin, Vincent Po Hen Lin, Ulla Milbreta, Jiah Shin Chin, Elaine Guo Yan Chew, Michelle Mulan Lian, Jia Nee Foo, Kunyu Zhang, Wutian Wu, Sing Yian Chew
Summary: A novel therapeutic approach for spinal cord injuries involving scaffold-mediated Axon miR treatment with methylprednisolone significantly enhances axon regeneration and functional recovery, while reducing inflammation gene expression.
Article
Chemistry, Multidisciplinary
Yongfeng Tao, Jan G. Felber, Zhongyu Zou, Evert Njomen, Jarrett R. Remsberg, Daisuke Ogasawara, Chang Ye, Bruno Melillo, Stuart L. Schreiber, Chuan He, David Remillard, Benjamin F. Cravatt
Summary: This study discovered azetidine acrylamides that act as covalent inhibitors of human NSUN2 through targeting a conserved catalytic cysteine, showing high isotype selectivity and perturbing NSUN2-tRNA interactions and the m5C content of RNA in cancer cells.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Analytical
Su Jiang, Qian Liu, Wen-Jing Liu, Lin Cui, Chun-Yang Zhang
Summary: A label-free fluorescent method has been developed to sensitively detect lncRNA in cancer cells. This method exhibits high sensitivity and potential for detecting different types of lncRNAs.
SENSORS AND ACTUATORS B-CHEMICAL
(2022)
Article
Cell Biology
Yuri Motorin, Mark Helm
Summary: RNA methylation has re-emerged as an important mechanism in gene regulation, leading to new insights in RNA research; the presence of methyltransferases in disease models and clinical investigations has significantly contributed to the field's progress; the concept of reversibility and dynamics in RNA modification has replaced the previous perception of irreversible RNA maturation, potentially resulting in diverse populations of RNA variants.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2022)
Editorial Material
Multidisciplinary Sciences
Mark Helm, Yuri Motorin
Summary: For the first time, a comprehensive study has described the phosphorylation in the core of a transfer RNA molecule and characterized the enzymes responsible for adding and removing the phosphate group.
Article
Biochemistry & Molecular Biology
Tim R. Fischer, Laurenz Meidner, Marvin Schwickert, Marlies Weber, Robert A. Zimmermann, Christian Kersten, Tanja Schirmeister, Mark Helm
Summary: RNA methyltransferases (MTases) are widely present enzymes that have gained increasing interest in the field of RNA methylation. This article discusses the development of small molecules for targeted transfer of functional groups and labels, as well as the investigation of SAM-derived compounds as inhibitors of RNA MTases.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Damien Bregeon, Ludovic Pecqueur, Sabrine Toubdji, Claudia Sudol, Murielle Lombard, Marc Fontecave, Valerie de Crecy-Lagard, Yuri Motorin, Mark Helm, Djemel Hamdane
Summary: Recent studies have revealed that RNA molecules undergo post-transcriptional modifications, including dihydrouridine modifications that were originally believed to be specific to tRNA. These modifications have been found not only in tRNA but also in mRNA, and they play important roles in meiotic chromosome segregation, protein translation rates, and cell proliferation. Dihydrouridine modifications are introduced by dihydrouridine synthases.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Elisabeth Kallert, Tim R. Fischer, Simon Schneider, Maike Grimm, Mark Helm, Christian Kersten
Summary: This study reveals the potential of protein-based docking programs to reproduce native binding modes of small-molecule RNA ligands and to distinguish known binders from decoys. A prospective virtual screening experiment demonstrates the feasibility of this approach.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Larissa Bessler, Navpreet Kaur, Lea-Marie Vogt, Laurin Flemmich, Carmen Siebenaller, Marie-Luise Winz, Francesca Tuorto, Ronald Micura, Ann E. Ehrenhofer-Murray, Mark Helm
Summary: This study successfully incorporated an azide-containing derivative into tRNA via transglycosylation, resulting in a semi-synthetic RNA modification called Q-L1. The incorporation of this clickable chemical entity was demonstrated in vitro and in vivo, indicating its functional integration into translation and recruitment to the ribosome. The Q-L1 modification facilitated analytics through click conjugation, and was shown to maintain tRNA substrate specificity and promote further modification in cellular systems. This study represents the first in vivo integration of a synthetic moiety into an RNA modification circuit.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Jasmin Hertler, Kaouthar Slama, Benedikt Schober, Zeynep Ozrendeci, Virginie Marchand, Yuri Motorin, Mark Helm
Summary: Techniques have been developed to isolate long, translatable, and internally point-modified mRNA, enabling functional analysis of these modified mRNAs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ivana Cavallin, Marek Bartosovic, Tomas Skalicky, Praveenkumar Rengaraj, Martin Demko, Martina Christina Schmidt-Dengler, Aleksej Drino, Mark Helm, Stepanka Vanacova
Summary: This study analyzed the RNA targets of ALKBH8 and found that ALKBH8 not only binds to a known set of tRNAs containing wobble U, but also to several other types of noncoding RNAs.
Article
Chemistry, Multidisciplinary
Larissa Bessler, Lea-Marie Vogt, Marc Lander, Christina Dal Magro, Patrick Keller, Jonas Kuehlborn, Christopher J. Kampf, Till Opatz, Mark Helm
Summary: Both RNA modification and RNA damage involve non-canonical nucleoside structures. While RNA modifications improve function, RNA damage has detrimental effects. This study identified and characterized a new structure, 2-methylthio-1,N6-ethenoadenosine (ms(2)epsilon A), related to a lesion resulting from exposure to alkylating chemicals. The formation of ms(2)epsilon A involves cleavage of a prenyl moiety in a known transfer RNA modification.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Florian Pichot, Marion C. Hogg, Virginie Marchand, Valerie Bourguignon, Elisabeth Jirstrom, Cliona Farrell, Hesham A. Gibriel, Jochen H. M. Prehn, Yuri Motorin, Mark Helm
Summary: Modification of tRNA is crucial for generating RNA expression diversity. In this study, the stoichiometry of incompletely modified sites in human tRNAs was investigated, and it was found that up to 75% of sites can be incompletely modified. The modification patterns of tRNA populations can provide information to differentiate different cell lines.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Chemistry, Medicinal
Robert Alexander Zimmermann, Marvin Schwickert, J. Laurenz Meidner, Zarina Nidoieva, Mark Helm, Tanja Schirmeister
Summary: This study explores the applicability of a novel fluorescent tracer for human RNA methyltransferase DNMT2 and establishes a new screening method using microscale thermophoresis. The results overcome some limitations of traditional methods and provide additional information.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)
Article
Chemistry, Medicinal
Marvin Schwickert, Robert A. Zimmermann, Tanja Habeck, Sabrina N. Hoba, Zarina Nidoieva, Tim R. Fischer, Martin M. Stark, Christian Kersten, Frederik Lermyte, Mark Helm, Tanja Schirmeister
Summary: The DNA methyltransferase 2 (DNMT2) is an RNA modifying enzyme that plays a role in various pathophysiological processes, including mental and metabolic disorders and cancer. In this study, covalent SAH-based DNMT2 inhibitors were developed and tested for their effectiveness. A 4-bromo-3-nitrophenylsulfonamide-decorated SAH derivative (80) was found to be the most potent and selective inhibitor, with confirmed covalent reaction with the catalytically active cysteine-79.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Review
Genetics & Heredity
Sylvain Delaunay, Mark Helm, Michaela Frye
Summary: Chemical modifications of nucleotides in RNA can alter its properties and are used for clinical purposes in stable artificial RNAs. These modifications also regulate cellular processes and their study has led to the understanding of disease mechanisms and innovative clinical approaches. The ability to manipulate RNA modifications offers therapeutic potential and has paved the way for novel clinical strategies.
NATURE REVIEWS GENETICS
(2023)
Article
Biochemical Research Methods
Anna Wierczeiko, Stefan Pastore, Stefan Muendnich, Anne M. Busch, Vincent Dietrich, Mark Helm, Tamer Butto, Susanne Gerber
Summary: Oxford Nanopore Technologies' sequencing platform allows for real-time analysis, providing early insights and accelerating decision-making for further analysis. NanopoReaTA is introduced as a user-friendly toolbox for real-time analysis of RNA-sequencing data from ONT, offering visual snapshots and enabling interactive sequencing and rapid decision-making.
Article
Biochemistry & Molecular Biology
Mark Helm, Markus T. Bohnsack, Thomas Carell, Alexander Dalpke, Karl-Dieter Entian, Ann Ehrenhofer-Murray, Ralf Ficner, Christian Hammann, Claudia Ho''bartner, Andres Ja''schke, Albert Jeltsch, Stefanie Kaiser, Roland Klassen, Sebastian A. Leidel, Andreas Marx, Mario Mo''rl, Jochen C. Meier, Gunter Meister, Andrea Rentmeister, Marina Rodnina, Jean-Yves Roignant, Raffael Schaffrath, Peter Stadler, Thorsten Stafforst
Summary: This article describes the impact and subsequent effects of the DFG-funded priority program SPP1784 on the field of nucleic acid modifications. The program has facilitated interdisciplinary collaborations and contributed to the development of the nucleic acid chemistry community. The extension of funding during the COVID-19 pandemic has led to increased interest and research in the field of RNA and RNA modifications, particularly in the context of vaccination campaigns against SARS-CoV-2.
ACS CHEMICAL BIOLOGY
(2023)