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
Sergey V. Pushkarev, Valeriia A. Vinnik, Irina V. Shapovalova, Vytas K. Svedas, Dmitry K. Nilov
Summary: This study used molecular dynamics simulations to identify the amino acid residues in the active site of tRNA-guanine transglycosylase that provide efficient binding of inhibitors. It was found that the ability of inhibitors to adopt a charged state in specific environments is crucial for complex formation. The study also predicted that the introduction of substituents would have different effects on inhibiting tRNA-guanine transglycosylase and DNA repair protein poly(ADP-ribose) polymerase 1.
BIOCHEMISTRY-MOSCOW
(2022)
Article
Biochemistry & Molecular Biology
Jorge Diaz-Rullo, Jose Eduardo Gonzalez-Pastor
Summary: In this study, we developed a novel bioinformatic strategy to predict Q-genes and found that these genes are widely enriched in cellular functions, especially in biofilm formation and virulence in bacteria, particularly in human pathogens. Experimental validation showed that altering the level of tRNA Q-modification significantly affected these physiological processes in different model bacteria, representing the first report of a general mechanism controlling biofilm formation and virulence in Gram-positive and Gram-negative bacteria. Additionally, we propose that changes in Q availability in a microbiome would impact its functionality. These findings open new avenues for the control of bacterial infections and biofilm formation by inhibiting tRNA Q-modification.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Yu Sun, Michael Piechotta, Isabel Naarmann-de Vries, Christoph Dieterich, Ann E. Ehrenhofer-Murray
Summary: This study utilized direct RNA sequencing with nanopore technology to detect queuosine modifications in tRNAs. The accuracy of the modifications was confirmed by comparing unmodified and modified tRNAs, and an improved protocol for alignment of raw sequence reads was presented. These findings enable further investigation into the biological function of tRNA modifications.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Sneha Kulkarni, Mary Anne T. Rubio, Eva Hegedusova, Robert L. Ross, Patrick A. Limbach, Juan D. Alfonzo, Zdenek Paris
Summary: Research revealed that in the protozoan parasite Trypanosoma brucei, Q-modified tRNAs have a preference for specific codons, which is crucial for mitochondrial protein synthesis and overall protein synthesis regulation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Katharina Sievers, Luisa Welp, Henning Urlaub, Ralf Ficner
Summary: This study reports the crystal structure of human TGT in its heterodimeric form and in complex with a 25-mer stem loop RNA, revealing detailed analysis of its dimer interface and interaction with a minimal substrate RNA. Through experiments and mutagenesis, the two-stranded beta E beta F-sheet of the QTRT2 subunit is identified as an important RNA-binding motif in the catalytically inactive subunit.
Review
Biochemistry & Molecular Biology
Valerie de Crecy-Lagard, Marshall Jaroch
Summary: Modified nucleotides in tRNA play a critical role in bacterial physiology, although their importance in translational regulation was previously overlooked. Recent breakthroughs in identifying tRNA modification genes and improving analytical tools have shed light on the key role of tRNA modifications in bacterial regulation. Through their decoding functions in translation and their link to metabolism, tRNA modifications are emerging as important components of the bacterial regulatory toolbox.
TRENDS IN MICROBIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Jilei Zhang, Yongguo Zhang, Callum J. McGrenaghan, Vincent P. Kelly, Yinglin Xia, Jun Sun
Summary: This study found that the expression of QTRT1 was significantly downregulated in patients with inflammatory bowel disease (IBD). The 4 Q-tRNA-related tRNA synthetases were also decreased in IBD patients. These changes were associated with alterations in epithelial cell proliferation and junction formation. Further investigation revealed that queuine treatment enhanced cell proliferation and junction activity, and reduced inflammation in epithelial cells. These findings uncover a novel role for tRNA modifications in the pathogenesis of IBD.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Multidisciplinary Sciences
Markus Hillmeier, Mirko Wagner, Timm Ensfelder, Eva Korytiakova, Peter Thumbs, Markus Mueller, Thomas Carell
Summary: The study introduces queuosine and its further modified derivatives, highlighting the differing structure of mannosyl-queuosine from the literature-reported one, showing an alpha-allyl connectivity.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Ember M. Tota, Neal K. Devaraj
Summary: Bacterial tRNA guanine transglycosylases (TGTs) can recognize and label specific DNA substrates, which expands the substrate scope of RNA transglycosylases to include DNA. The minimal sequence requirements for transglycosylation of unmodified DNA by E. coli TGT have been determined, and controlling steric constraint in the DNA hairpin significantly affects labeling efficiency. The newly developed DNA-TAG system allows for the rapid synthesis of probes for various applications.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Qiang Li, Remi Zallot, Brian S. MacTavish, Alvaro Montoya, Daniel J. Payan, You Hu, John A. Gerlt, Alexander Angerhofer, Valerie De Crecy-Lagard, Steven D. Bruner
Summary: This study reveals the final step of queuosine biosynthesis and demonstrates new diversity in the chemistry of iron/sulfur-dependent enzymes, providing novel insights into the mechanism of these widely conserved tRNA modifications.
Article
Biochemistry & Molecular Biology
Christopher D. Katanski, Christopher P. Watkins, Wen Zhang, Matthew Reyer, Samuel Miller, Tao Pan
Summary: Queuosine (Q) is a tRNA modification that plays important roles in translation efficiency and fidelity. By using a method called periodate-treatment, Q modification in RNA samples can be analyzed at single base resolution. This method also enables the detection of other modifications. This method, called PAQS-seq, is widely applicable in studying the roles of Q and other modifications in mammalian and microbial tRNAs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Maurice Sebastiani, Christina Behrens, Stefanie Doerr, Hans-Dieter Gerber, Rania Benazza, Oscar Hernandez-Alba, Sarah Cianferani, Gerhard Klebe, Andreas Heine, Klaus Reuter
Summary: The modified nucleoside queuosine affects translation speed and accuracy in tRNA(Asp), tRNA(Asn), tRNA(Tyr), and tRNA(His) of bacteria and eukaryotes. Eukaryotes obtain queuine as a micronutrient from food and/or the gut microbiome since they cannot synthesize queuosine de novo. The enzyme tRNA-guanine transglycosylase (TGT) catalyzes the insertion of queuine into these tRNAs, and its crystal structures and reaction mechanism have been studied to understand its medical potential, particularly in the treatment of multiple sclerosis and breast cancer.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Natalie Krahn, Jingji Zhang, Sergey Melnikov, Jeffery M. Tharp, Alessandra Villa, Armaan Patel, Rebecca J. Howard, Haben Gabir, Trushar R. Patel, Jorg Stetefeld, Joseph Puglisi, Dieter Soll
Summary: Protein translation is achieved through tRNA aminoacylation and ribosomal elongation. This study explores the tRNA identity elements for a Delta pylSn tRNA(Pyl) and identifies five key elements necessary for MaPylRS activity.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Zhaoli Yu, Zihan Wu, Ye Li, Qiang Hao, Xiaofeng Cao, Gregor M. Blaha, Jinzhong Lin, Guoliang Lu
Summary: Two types of glycyl-tRNA synthetase (GlyRS) have been identified, alpha(2) and alpha(2)beta(2) GlyRSs. While the mechanisms for alpha(2) GlyRSs are well understood, little is known about the mechanisms for alpha(2)beta(2)/(alpha beta)(2) GlyRSs. This study presents the structures of the (alpha beta)(2) GlyRS from Oryza sativa chloroplast, revealing a complex mechanism of tRNA selection and access to the active site.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Martin Mueller, Carine Legrand, Francesca Tuorto, Vincent P. Kelly, Yaser Atlasi, Frank Lyko, Ann E. Ehrenhofer-Murray
NUCLEIC ACIDS RESEARCH
(2019)
Article
Biochemistry & Molecular Biology
Jill Browning, Michael Rooney, Emily Hams, Satoru Takahashi, Seiya Mizuno, Fumihiro Sugiyama, Padraic G. Fallon, Vincent P. Kelly
MOLECULAR BIOLOGY REPORTS
(2020)
Article
Nutrition & Dietetics
Patti Hayes, Claire Fergus, Magda Ghanim, Cansu Cirzi, Lyubomyr Burtnyak, Callum J. McGrenaghan, Francesca Tuorto, Derek P. Nolan, Vincent P. Kelly
Article
Chemistry, Medicinal
A. Prasanth Saraswati, Nicola Relitti, Margherita Brindisi, Jeremy D. Osko, Giulia Chemi, Stefano Federico, Alessandro Grillo, Simone Brogi, Niamh H. McCabe, Richard C. Turkington, Ola Ibrahim, Jeffrey O'Sullivan, Stefania Lamponi, Magda Ghanim, Vincent P. Kelly, Daniela Zisterer, Rebecca Amet, Patricia Hannon Barroeta, Francesca Vanni, Cristina Ulivieri, Daniel Herp, Federica Sarno, Antonella Di Costanzo, Fulvio Saccoccia, Giovina Ruberti, Manfred Jung, Lucia Altucci, Sandra Gemma, Stefania Butini, David W. Christianson, Giuseppe Campiani
ACS MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Biochemistry & Molecular Biology
Koen van Wijk, Takeru Akabane, Tomohiro Kimura, Shinichi Saitoh, Satoshi Okano, Vincent P. Kelly, Michiaki Takagi, Ken Kodama, Kiwamu Takahashi, Tohru Tanaka, Motowo Nakajima, Osamu Nakajima
Summary: This study found an age-dependent reduction in free heme levels in the skeletal muscle and liver of ALAS1 heterozygous mice, while there was only a slight decrease in the liver of WT mice. Total heme levels did not show significant differences between young and aged mice. ALAS1 mRNA levels exhibited an age-dependent reduction similar to the free heme levels.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
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
Multidisciplinary Sciences
Magda Ghanim, Nicola Relitti, Gavin McManus, Stefania Butini, Andrea Cappelli, Giuseppe Campiani, K. H. Mok, Vincent P. Kelly
Summary: CD44 as an important receptor biomarker for oral cancer, the water-soluble fluorescent probe compound 1 shows promising potential for real-time intraoperative imaging due to its reversible and non-toxic nature.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Ciara G. Doran, Ryoichi Sugisawa, Michael Carty, Fiona Roche, Claire Fergus, Karsten Hokamp, Vincent P. Kelly, Andrew G. Bowie
Summary: Investigations into the gene expression of SARM1 in macrophages have revealed its roles in neuronal degeneration and immunity. The generation of Sarm1-/- mice and epitope-tagged SARM1 mice have provided further insights into the transcriptional regulation and functional aspects of SARM1 in macrophages and neurons.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Ciara M. McDonnell, Magda Ghanim, J. Mike Southern, Vincent P. Kelly, Stephen J. Connon
Summary: This study investigates the impact of modified beta-lysines on the growth rates of eubacterial cells. The results indicate that the observed effects are due to the post translational modification of Elongation Factor P (EFP) catalyzed by PoxA. The promiscuity of PoxA allows for examination of a wide range of exogenous beta-lysines.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Giuseppe Campiani, Tuhina Khan, Cristina Ulivieri, Leopoldo Staiano, Chiara Papulino, Stefania Magnano, Seema Nathwani, Anna Ramunno, Daniel Lucena-Agell, Nicola Relitti, Stefano Federico, Luca Pozzetti, Gabriele Carullo, Alice Casagni, Simone Brogi, Francesca Vanni, Paola Galatello, Magda Ghanim, Niamh McCabe, Stefania Lamponi, Massimo Valoti, Ola Ibrahim, Jeffrey O'Sullivan, Richard Turkington, Vincent P. Kelly, Ruben VanWemmel, J. Fernando Diaz, Sandra Gemma, Daniela Zisterer, Lucia Altucci, Antonella De Matteis, Stefania Butini, Rosaria Benedetti
Summary: Autophagy, a crucial mechanism for maintaining organismal homeostasis, has become a focus in cancer therapy. In this study, new multifunctional agents with both pro-apoptotic and autophagy-inhibiting effects were designed and their therapeutic potential was demonstrated through experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Johannes A. Sake, Mohammed Ali Selo, Lyubomyr Burtnyak, Henriette E. Dahnhardt, Camelia Helbet, Severin Mairinger, Oliver Langer, Vincent P. Kelly, Carsten Ehrhardt
Summary: Multidrug resistance-associated protein 1 (MRP1/ABCC1) is an efflux transporter responsible for the extrusion of endogenous substances as well as xenobiotics and their respective metabolites. The generation of an ABCC1-/- clone based on the human distal lung epithelial cell line NCI-H441 via a targeted CRISPR/Cas9 approach provides a useful tool to study MRP1 function in vitro. The ABCC1-/- NCI-H441 clone showed complete absence of mRNA and protein, and retained the ability to form electrically tight barriers.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Shr-Hau Hung, Gregory Elliott, Thakku R. Ramkumar, Lyubomyr Burtnyak, Callum J. McGrenaghan, Sana Alkuzweny, Samia Quaiyum, Dirk Iwata-Reuyl, Xiaobei Pan, Brian D. Green, Vincent P. Kelly, Valerie De Crecy-Lagard, Manal A. Swairjo
Summary: Eukaryotic life relies on bacteria for the biosynthesis and supply of vitamins and micronutrients, including the micronutrient queuosine. The hydrolase enzyme QNG1 plays a crucial role in releasing queuine from queuosine-5'-monophosphate, which is essential for various physiological processes associated with queuine deficiency, such as metabolism, proliferation, differentiation, and cancer progression.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Gastroenterology & Hepatology
Jilei Zhang, Yongguo Zhang, Callum J. McGrenaghan, Vincent P. Kelly, Yinglin Xia, Jun Sun
Summary: This study found that the expression of QTRT1 was significantly downregulated in patients with inflammatory bowel disease (IBD). The 4 Q-tRNA-related tRNA synthetases were also decreased in IBD patients. These changes were associated with alterations in epithelial cell proliferation and junction formation. Further investigation revealed that queuine treatment enhanced cell proliferation and junction activity, and reduced inflammation in epithelial cells. These findings uncover a novel role for tRNA modifications in the pathogenesis of IBD.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Meeting Abstract
Hematology
Aoife Yeow, Ciara Byrne, Heike Hawerkamp, Anne Chevalier, Laura Matarazzo, Jamie M. O'Sullivan, Vincent Kelly, Bagirath Gangadharan, BirgitM. Reipert, James O'Donnell, Peter Turecek, Padraic Fallon
Article
Chemistry, Multidisciplinary
Mashael A. Alqasem, Claire Fergus, J. Mike Southern, Stephen J. Connon, Vincent P. Kelly
CHEMICAL COMMUNICATIONS
(2020)