Article
Biochemistry & Molecular Biology
Tatsuaki Kurata, Tetiana Brodiazhenko, Sofia Raquel Alves Oliveira, Mohammad Roghanian, Yuriko Sakaguchi, Kathryn Jane Turnbull, Ondrej Bulvas, Hiraku Takada, Hedvig Tamman, Andres Ainelo, Radek Pohl, Dominik Rejman, Tanel Tenson, Tsutomu Suzuki, Abel Garcia-Pino, Gemma Catherine Atkinson, Vasili Hauryliuk
Summary: Multiple families of SAS RSH enzymes have been discovered to inhibit bacterial growth by specifically inhibiting protein synthesis, establishing RSHs as RNA-modifying enzymes.
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
Biochemistry & Molecular Biology
Jerneja Tomsic, Enrico Caserta, Cynthia L. Pon, Claudio O. Gualerzi
Summary: The substitution of a conserved histidine in the guanosine nucleotide binding domain of Escherichia coli translation initiation factor IF2 resulted in impaired ribosome-dependent GTPase activity, leading to severe protein synthesis inhibition and a dominant lethal phenotype. Reduced affinities of IF2 for ribosomes and fMet-tRNA were found to suppress this lethality, indicating that the conformational changes during translation initiation are thermally driven and energy from IF2-dependent GTP hydrolysis is not necessary for successful initiation. The dissociation of the interaction between IF2 C2 and fMet-tRNA was identified as the rate-limiting step for productive P site alignment and IF2 release from the ribosome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Nihar Ranjan, Dev P. Arya
Summary: G-quadruplex-forming nucleic acids have diverse applications in biology, drug design, sensing, and nanotechnology. We demonstrate that neomycin can bind to parallel G-quadruplexes with affinities in the range of Ka & SIM; 105-108 M-1, depending on various factors. These findings expand the binding landscape of neomycin and offer new insights for the design of high-affinity neomycin-based G-quadruplex binders.
FRONTIERS IN CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Takayuki Katoh, Hiroaki Suga
Summary: Using a chimeric initiator tRNA and EF-P can effectively suppress the N-terminal drop-off event induced by noncanonical initiator substrates, leading to the synthesis of full-length peptides. By optimizing translation conditions, complete suppression of exotic amino acids and up to a 1000-fold increase in expression level of full-length peptides can be achieved.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Genetics & Heredity
Monika Tasak, Eric M. Phizicky
Summary: All tRNAs require modifications for proper function, and lack of these modifications can lead to growth defects and disorders. This study found that specific tRNA body modifications are necessary for tRNA stability and function, and mutants lacking these modifications target hypomodified tRNAs to rapid decay pathways. These findings suggest the importance of these modifications for tRNA biology in different organisms.
Article
Microbiology
Aude Trinquier, Ciaran Condon, Frederique Braun
Summary: The passage of ribosomes during translation can have varied effects on mRNA degradation, ranging from protection to susceptibility to RNase. The availability of functional tRNA plays a significant role in the stability of some assembly-related mRNAs. Depleting tRNA maturation enzymes leads to altered mRNA levels in assembly factors.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Haaris A. Safdari, Sergo Kasvandik, Christine Polte, Zoya Ignatova, Tanel Tenson, Daniel N. Wilson
Summary: The heat shock protein 15 (Hsp15) in bacteria has different binding sites and mechanisms compared to its homolog RqcP in Bacillus subtilis. Our study found that Hsp15 in Escherichia coli binds to the 50S subunit upon heat shock, stabilizes the peptidyl-tRNA in the P-site, and promotes the release of aberrant nascent polypeptide chains.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Ritwika S. Basu, Michael B. Sherman, Matthieu G. Gagnon
Summary: During translation initiation, IF2 holds fMet-tRNA(i)(fMet) in the P site and facilitates the transition of the ribosome to the elongation phase. Our study reveals the mechanism of separation between IF2 and initiator tRNA and provides insights into the regulation of ribosome during translation elongation.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Isao Masuda, Jae-Yeon Hwang, Thomas Christian, Sunita Maharjan, Fuad Mohammad, Howard Gamper, Allen R. Buskirk, Ya-Ming Hou
Summary: N-1-methylation of G37 is crucial for maintaining the translational reading-frame of a subset of tRNAs, with its deficiency leading to ribosome stalling during decoding of affected codons and affecting tRNA aminoacylation and peptide-bond formation. This study highlights a previously unrecognized role of m(1) G37 throughout the elongation cycle of protein synthesis, shedding light on its essentiality for bacterial growth and survival.
Article
Microbiology
Neeraja Marathe, Ha An Nguyen, John N. Alumasa, Alexandra B. Kuzmishin Nagy, Michael Vazquez, Christine M. Dunham, Kenneth C. Keiler
Summary: This study reports a small molecule inhibitor called KKL-55 that specifically targets the interaction between EF-Tu and tmRNA, inhibiting bacterial translation without affecting normal translation. This discovery provides a potential avenue for developing new antibiotics to treat drug-resistant infections.
Article
Multidisciplinary Sciences
Panagiotis Poulis, Anoshi Patel, Marina V. Rodnina, Sarah Adio
Summary: Slippery sequences in mRNA can cause the ribosome to change its reading frame, affecting the translation process. Research has shown that during translocation on slippery sequences, the ribosome switches from a fast and accurate translation mode to a slow and frameshifting-prone mode, reducing translation fidelity.
NATURE COMMUNICATIONS
(2022)
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
Howard Gamper, Haixing Li, Isao Masuda, D. Miklos Robkis, Thomas Christian, Adam B. Conn, Gregor Blaha, E. James Petersson, Ruben L. Gonzalez, Ya-Ming Hou
Summary: The study investigates the translation of quadruplet codons by a +1-frameshifting tRNA SufB2, revealing that SufB2 initially uses triplet anticodon-codon pairing in the 0-frame to decode the quadruplet codon before shifting to the +1-frame during tRNA-mRNA translocation. The frameshifting mechanism of SufB2 involves perturbation of a crucial ribosome conformational change, highlighting the potential for engineering specific ribosome conformational changes to enhance genome recoding efficiency.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Jing Wang, Yuka Yashiro, Yuriko Sakaguchi, Tsutomu Suzuki, Kozo Tomita
Summary: CdiA-CTEC869 cleaves specific tRNAs by interacting with translation factors Tu and Ts, and interacts with domain II of Tu to affect the structure and cleavage efficiency of tRNAs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Aleksandra V. Petrovskaya, Artem M. Tverskoi, Evgeny P. Barykin, Kseniya B. Varshavskaya, Alexandra A. Dalina, Vladimir A. Mitkevich, Alexander A. Makarov, Irina Yu. Petrushanko
Summary: The breakdown of the blood-brain barrier in Alzheimer's disease promotes the accumulation of beta-amyloid peptide in the brain. Different forms of this peptide have varying effects on the redox status and mitochondrial function of brain endothelial cells, which play a role in BBB breakdown.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Dermatology
Helen Vaher, Kristiina Kingo, Peep Kolberg, Martin Pook, Liisi Raam, Anet Laanesoo, Anu Remm, Tanel Tenson, Kaur Alasoo, Ulrich Mrowietz, Stephan Weidinger, Kulli Kingo, Ana Rebane
Summary: The study confirms the alteration in expression of IL-1 family cytokines and inflammasome-related genes in the development of atopic dermatitis (AD), and a positive relationship between NLRP1 and IL1B or IL18 mRNA levels. It also demonstrates increased expression of NLRP1 and PYCARD proteins, and increased caspase-1 activity in the skin of AD patients. Additionally, genetic associations with AD and the involvement of various immune cell types are predicted. In keratinocytes, colonization with Staphylococcus aureus results in increased secretion of IL-1b and IL-18, which is inhibited by siRNA silencing of NLRP1. These findings suggest that S. aureus colonization may activate the NLRP1 inflammasome in keratinocytes, leading to the secretion of IL-1b and IL-18, and contributing to the pathogenesis of AD, particularly in the presence of genetic variations in the IL-18 pathway.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Kairi Lorenz, Liis Preem, Kadi Sagor, Marta Putrins, Tanel Tenson, Karin Kogermann
Summary: Increasing evidence suggests that chronic wounds are associated with bacterial biofilms. New wound care products are being developed to inhibit biofilm formation and treat existing ones. In order to analyze these new antibacterial drug delivery systems, standardized assays and appropriate tools and models are needed. This study demonstrates that optimized in vitro and ex vivo wound infection and biofilm models provide a convenient approach for testing the antibacterial and antibiofilm properties of novel wound dressings. The results can be used to design more effective wound care products and screen different formulations and active substances.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Hedvig Tamman, Karin Ernits, Mohammad Roghanian, Andres Ainelo, Christina Julius, Anthony Perrier, Ariel Talavera, Hanna Ainelo, Remy Dugauquier, Safia Zedek, Aurelien Thureau, Javier Perez, Gipsi Lima-Mendez, Regis Hallez, Gemma C. Atkinson, Vasili Hauryliuk, Abel Garcia-Pino
Summary: Stringent factors regulate bacterial cell reprogramming by increasing the level of (p)ppGpp. This study presents the crystal structure of the hydrolase-only SpoT from Acinetobacter baumannii and reveals the intramolecular regulation mechanism of 'long'-stringent factors. The Core subdomain plays a key role in determining the specialization of long RelA-SpoT homologs towards synthesis or hydrolysis.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Andres Ainelo, Julien Caballero-Montes, Ondrej Bulvas, Karin Ernits, Kyo Coppieters't Wallant, Hiraku Takada, Sophie Z. Craig, Gabriel Mazzucchelli, Safia Zedek, Iva Pichova, Gemma C. Atkinson, Ariel Talavera, Chloe Martens, Vasili Hauryliuk, Abel Garcia-Pino
Summary: In this study, the crystal structure of the DarB2:RelNTD2 complex was determined to uncover how DarB interacts with the SYNTH domain of Rel to stimulate (p)ppGpp synthesis directly. Binding to c-di-AMP rigidifies DarB, imposing an entropic penalty that precludes DarB-mediated control of Rel during normal growth. These experiments provide insights into the allosteric regulation mechanism of Rel stringent factors independent of amino acid starvation.
Article
Biochemistry & Molecular Biology
Viktoriia E. Baksheeva, Veronika V. Tiulina, Elena N. Iomdina, Sergey Yu. Petrov, Olga M. Filippova, Nina Yu. Kushnarevich, Elena A. Suleiman, Remi Eyraud, Francois Devred, Marina V. Serebryakova, Natalia G. Shebardina, Dmitry V. Chistyakov, Ivan I. Senin, Vladimir A. Mitkevich, Philipp O. Tsvetkov, Evgeni Yu. Zernii
Summary: Primary open-angle glaucoma (POAG) is a common neurodegenerative disorder that causes blindness and is characterized by optic nerve and retinal ganglion cell damage. Early detection and treatment of the disease are crucial, but difficult due to its asymptomatic nature and lack of objective diagnostic approaches. Recent studies have shown that glaucoma involves complex metabolomic and proteomic changes in eye liquids, including tear fluid. However, the analysis of tear fluid is technically challenging and not suitable for clinical practice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yaroslava M. M. Chalenko, Daria A. A. Slonova, Olga I. I. Kechko, Egor V. V. Kalinin, Vladimir A. A. Mitkevich, Svetlana A. A. Ermolaeva
Summary: The virulence factor InlB of Listeria monocytogenes interacts specifically with the receptors c-Met and gC1q-R. This study examines the effects of different isoforms of InlB on L. monocytogenes uptake and intracellular proliferation in human macrophages. The isoform idInlB(CC1) exhibits the highest efficiency in macrophage proliferation compared to other isoforms. Pretreatment of macrophages with idInlB(CC1) impairs macrophage functions, decreasing pathogen uptake and improving its intracellular multiplication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Nozomu Obana, Hiraku Takada, Caillan Crowe-McAuliffe, Mizuki Iwamoto, Artyom A. Egorov, Kelvin J. Y. Wu, Shinobu Chiba, Victoriia Murina, Helge Paternoga, Ben I. C. Tresco, Nobuhiko Nomura, Andrew G. Myers, Gemma C. Atkinson, Daniel N. Wilson, Vasili Hauryliuk
Summary: This study investigates genome-encoded antibiotic resistance ABC proteins from different bacteria and discovers their resistance spectrum and mechanisms, which are important for understanding the diversity of intrinsic antibiotic resistance in bacteria.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Engineering, Environmental
Veljo Kisand, Peeter Laas, Kadi Palmik-Das, Kristel Panksep, Helen Tammert, Leena Albreht, Hille Allemann, Lauri Liepkalns, Katri Vooro, Christian Ritz, Vasili Hauryliuk, Tanel Tenson
Summary: Taking advantage of Estonia's small size and population, a wastewater-based epidemiology approach was used to monitor the spread of SARS-CoV-2, with weekly nation-wide updates released. Results showed that the concentration of the virus in wastewater correlated with the number of COVID-19 infections in the population, and the increase in virus concentration preceded the increase in positive cases by approximately 1.25 weeks (9 days). The surveillance system in Estonia helped inform public health policies and interventions during the COVID-19 pandemic.
Article
Biochemistry & Molecular Biology
Taavi Pall, Hannes Luidalepp, Tanel Tenson, Ulo Maivali
Summary: We evaluated the quality of inferential statistics in the field of differential expression profiling using high-throughput sequencing (HT-seq) by analyzing datasets submitted to the NCBI GEO data repository from 2008 to 2020. Our findings indicate widespread bias and unreliability of statistical methods used to analyze HT-seq data. Only a small percentage of experiments resulted in expected p-value distributions, and many experiments showed indications of differential expression despite assumptions that most genes are not differentially expressed. The choice of differential expression analysis program also influenced the observed patterns.
Article
Microbiology
Anna Maria Giuliodori, Riccardo Belardinelli, Melodie Duval, Raffaella Garofalo, Emma Schenckbecher, Vasili Hauryliuk, Eric Ennifar, Stefano Marzi
Summary: Escherichia coli CspA is an RNA binding protein that stimulates translation, including its own, during cold-shock. It specifically promotes the translation of cspA mRNA at low temperature by interacting with the folded conformation less accessible to the ribosome without inducing large structural rearrangements. This interaction allows the progression of ribosomes during the transition from translation initiation to elongation, and a similar mechanism may be responsible for CspA-dependent translation stimulation observed with other probed mRNAs.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Janani Durairaj, Andrew M. Waterhouse, Toomas Mets, Tetiana Brodiazhenko, Minhal Abdullah, Gabriel Studer, Gerardo Tauriello, Mehmet Akdel, Antonina Andreeva, Alex Bateman, Tanel Tenson, Vasili Hauryliuk, Torsten Schwede, Joana Pereira
Summary: The AlphaFold database provides millions of predicted protein structures, covering almost all known proteins. By utilizing deep learning techniques, these structures can be accurately predicted, shedding light on the functions and roles of these proteins in biology. This study further explores the discovery of new protein families through these predicted structures.
Article
Biochemical Research Methods
Lucia Dominguez-Molina, Ariel Talavera, Albinas Cepauskas, Tatsuaki Kurata, Dannele Echemendia-Blanco, Vasili Hauryliuk, Abel Garcia-Pino
Summary: This study reports the production, biophysical analysis, and crystallization of the aTfaRel2/faRel2 operon from Coprobacillus sp. D7, which encodes a bicistronic type II toxin-antitoxin module. The structures of the antitoxin ATfaRel2, toxin FaRel2, and the ATfaRel2-FaRel2 complex were determined through crystallography. These findings provide insights into the structure and function of this TA module.
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2023)
Article
Microbiology
Lucille Rudin, Noelle Roth, Julien Kneubuehler, Badri Nath Dubey, Michael M. Bornstein, Viktoriya Shyp
Summary: This study found that luteolin, a natural compound, has potent anti-biofilm properties against Streptococcus mutans, a key cariogenic pathogen. Luteolin inhibits biofilm formation and acid production, reduces the expression of virulence genes, and does not affect bacterial cell viability.
MICROBIOLOGY SPECTRUM
(2023)
