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
Microbiology
Daniel Goncalves-Carneiro, Paul D. Bieniasz
Summary: The development of safe and effective vaccines against viruses is crucial for disease control. Recent advancements in DNA synthesis technology have fueled research efforts in generating attenuated viruses through synonymous mutations. Understanding the molecular mechanisms of attenuation by genetic recoding of viruses could provide insights for vaccine development.
Review
Biotechnology & Applied Microbiology
Jeff Coller, Zoya Ignatova
Summary: Transfer RNAs have a crucial role in protein synthesis and their therapeutic potential for treating genetic diseases is gaining attention. Engineering tRNAs can restore protein synthesis, while supplementation of natural tRNAs can counteract missense mutations. However, challenges in tRNA efficacy, delivery systems, and manufacturing need to be addressed.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Article
Microbiology
Maxime Fages-Lartaud, Martin Frank Hohmann-Marriott
Summary: The compact translation machinery of chloroplasts makes them a promising platform for biotechnological innovation. In this study, we synthesize all available information on tRNA modifications in chloroplasts and assess translation efficiency for each modified anticodon-codon pair. We also analyze the enzymes associated with tRNA modifications and aminoacylation in Chlamydomonas reinhardtii chloroplasts. This work provides a comprehensive analysis of codon and anticodon interactions in chloroplasts and their implications for translation efficiency.
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
Biochemistry & Molecular Biology
Rhondene Wint, Asaf Salamov, Igor Grigoriev
Summary: Protein-coding genes have evolved a preference for codon usage as a result of both adaptive and nonadaptive influences. Comparative genomics analysis of over 450 species suggests that codon usage and tRNAs are coadapted for translation speed, likely a form of convergent evolution. Phylogenetic reconstruction indicates that adaptive radiation is a better explanation for the variation in interspecific codon usage bias than genetic drift.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Multidisciplinary Sciences
Michael Yarus
Summary: The study showed that minimally evolved codes retain qualities of the standard genetic code but constrain the possibility of evolution. The shape and size of wobble domains significantly affect the accuracy of codon assignments. Additionally, a plausible pathway to limited randomness is necessary to fit a highly ordered, degenerate code into a preset three-dimensional space.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Amila Zuko, Moushami Mallik, Robin Thompson, Emily L. Spaulding, Anne R. Wienand, Marije Been, Abigail L. D. Tadenev, Nick van Bakel, Celine Sijlmans, Leonardo A. Santos, Julia Bussmann, Marica Catinozzi, Sarada Das, Divita Kulshrestha, Robert W. Burgess, Zoya Ignatova, Erik Storkebaum
Summary: Heterozygous mutations in six transfer RNA synthetase genes cause Charcot-Marie-Tooth peripheral neuropathy. Mutant tRNA synthetases in CMT inhibit protein synthesis by binding tRNA(Gly) but failing to release it, leading to tRNAGly sequestration and ribosome stalling. Overexpression of tRNA(Gly) rescues protein synthesis, peripheral neuropathy, and ISR activation, suggesting therapeutic potential in CMT2D.
Article
Multidisciplinary Sciences
Ambar Kachale, Zuzana Pavlikova, Anna Nenarokova, Adriana Roithova, Ignacio M. Durante, Petra Miletinova, Kristina Zahonova, Serafim Nenarokov, Jan Votypka, Eva Horakova, Robert L. Ross, Vyacheslav Yurchenko, Petra Beznoskova, Zdenek Paris, Leos Shivaya Valasek, Julius Lukes
Summary: The study discovered that Blastocrithidia nonstop, a protist, lacks in-frame stop codons in its genes. It is believed that UGA was previously a stop codon, but has now been reprogrammed as a tryptophan codon due to a deficiency in one of the bases. A mutation in a gene called B. nonstop release factor 1 was also found to restrict recognition of UGA, thereby enhancing its reassignment.
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
Han-Kai Jiang, Nicole L. Ambrose, Christina Z. Chung, Yane-Shih Wang, Dieter Soll, Jeffery M. Tharp
Summary: Synthetic biology tools have been developed to control gene expression at the transcription level, but few methods exist for regulating gene expression at the translational level. In this study, split orthogonal aminoacyl-tRNA synthetases (o-aaRS) were designed to control gene translation in bacteria and mammalian cells. These split o-aaRSs function as genetically encoded AND gates, where stop codon suppression is controlled by two distinct molecular inputs. Additionally, they can be used as versatile biosensors to detect protein-protein interactions involved in cancer and SARS-CoV-2 infection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Yekaterina Shulgina, Sean R. Eddy
Summary: The genetic code, once thought to be a 'frozen accident,' has been found to evolve to some extent through the discovery of alternative genetic codes. The development of a computational method called Codetta allowed the prediction of amino acid decoding from nucleotide sequence data. By analyzing over 250,000 bacterial and archaeal genome sequences, five new codon reassignments for arginine were discovered, with evolutionary forces like low GC content driving these changes. The study demonstrates the utility of Codetta in understanding how genetic codes evolve and ensuring accuracy in protein databases.
Article
Biochemistry & Molecular Biology
Pawel Blazej, Konrad Pawlak, Dorota Mackiewicz, Pawel Mackiewicz
Summary: This study investigates the evolutionary mechanisms of codon block structure in the genetic code through computer simulations. The results demonstrate that the reading system similar to that present in the standard genetic code (SGC) quickly dominates during evolution and possesses similar characteristics to the SGC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Michael Shaferman, Melis Gencel, Noga Alon, Khawla Alasad, Barak Rotblat, Adrian W. R. Serohijos, Lital Alfonta, Shimon Bershtein
Summary: The variability in codon bias between bacterial genomes can interfere with horizontal gene transfer, which drives bacterial adaptation. This study designed an experimental system to investigate the constraints imposed by codon bias on the integration of transferred genes. It was found that mRNA folding stability plays a dominant role in fitness contribution when horizontal gene transfer leads to overstabilization of the 5'-end mRNA.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Multidisciplinary Sciences
Thibault Latrille, Nicolas Rodrigue, Nicolas Lartillot
Summary: Adaptation in protein-coding sequences can be detected using either multiple sequence alignments across species or polymorphism data within a population. Traditional phylogenetic codon models have limitations due to purifying selection, but recent developments in mutation-selection codon models provide a more detailed assessment of mutation, purifying, and positive selection. This exome-wide analysis shows that proteins and sites detected to be under adaptation at the phylogenetic scale are also under adaptation at the population-genetic scale, reconciling the two approaches and enabling integrative models and analyses across individuals and populations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Letter
Cell Biology
Xiaoyun Wang, Yan Li, Wenjun Chen, Hailing Shi, A. Murat Eren, Aleksey Morozov, Chuan He, Guan-Zheng Luo, Tao Pan
Article
Biochemical Research Methods
Mridusmita Saikia, Philip Burnham, Sara H. Keshavjee, Michael F. Z. Wang, Michael Heyang, Pablo Moral-Lopez, Meleana M. Hinchman, Charles G. Danko, John S. L. Parker, Iwijn De Vlaminck
Article
Multidisciplinary Sciences
Rui Xi, Preetish Kadur Lakshminarasimha Murthy, Kuei-Ling Tung, Cynthia D. Guy, Ji Wan, Feng Li, Zhuo Wang, Xiaodong Li, Anastasia Varanko, Nikolai Rakhilin, Yongning Xin, Botao Liu, Shu-Bing Qian, Lishan Su, Yan Han, Xiling Shen
Correction
Biochemistry & Molecular Biology
Honghui Ma, Xiaoyun Wang, Jiabin Cai, Qing Dai, S. Kundhavai Natchiar, Ruitu Lv, Kai Chen, Zhike Lu, Hao Chen, Yujiang Geno Shi, Fei Lan, Jia Fan, Bruno P. Klaholz, Tao Pan, Yang Shi, Chuan He
NATURE CHEMICAL BIOLOGY
(2019)
Article
Biochemical Research Methods
Yilin Ye, Jian Wang, Yunwan Xu, Yi Wang, Youdong Pan, Qi Song, Xing Liu, Ji Wan
Summary: Our study presents a pan-allele HLA-peptide binding prediction framework-MATHLA, which integrates bi-directional long short-term memory network and multiple head attention mechanism. This model shows better prediction accuracy in both fivefold cross-validation test and independent test dataset. Additionally, the model outperforms existing tools in predicting longer ligands ranging from 11 to 15 amino acids and demonstrates significant improvement in HLA-C-peptide-binding prediction.
BMC BIOINFORMATICS
(2021)
Article
Medicine, Research & Experimental
Mridusmita Saikia, Marlena M. Holter, Leanne R. Donahue, Isaac S. Lee, Qiaonan C. Zheng, Journey L. Wise, Jenna E. Todero, Daryl J. Phuong, Darline Garibay, Reilly Coch, Kyle W. Sloop, Adolfo Garcia-Ocana, Charles G. Danko, Bethany P. Cummings
Summary: Studies have shown that liraglutide, a GLP-1 receptor agonist, can increase alpha cell GLP-1 expression in a beta cell GLP-1R-dependent manner, providing potential new targets for diabetes treatment.
Article
Biochemistry & Molecular Biology
Jia Huang, Wenjun Chen, Fan Zhou, Zhichang Pang, Luoluo Wang, Tao Pan, Xiaoyun Wang
Summary: This study investigated the interplay between the microbiome and host tRNA profiles, revealing tissue-specific and microbiome-dependent reprogramming of tRNA expression and modifications. The intestines and brains were found to be more sensitive to microbiome influence in terms of tRNA expression, while cytosolic tRNAs in the livers and kidneys showed more obvious changes in tRNA modifications in the presence of the microbiome. These findings highlight a previously unexplored relationship among the microbiome, tRNA abundance, and epitranscriptome in a mammalian host.
Article
Biochemistry & Molecular Biology
Fan Zhou, Biaodi Liu, Xin Liu, Yan Li, Luoluo Wang, Jia Huang, Guanzheng Luo, Xiaoyun Wang
Summary: This study investigated the impact of microbiome and microbiota-derived sodium butyrate on host transcriptome and metabolome using Drosophila model. The results demonstrated that sodium butyrate can influence host gene expression patterns and gut bacterial structures, with lipids being the dominant changed components in Drosophila metabolites. The integrative analysis of multi-omics data identified candidate transcripts coregulated by sodium butyrate, enhancing the understanding of host-microbiome interactions at a molecular level.
Article
Microbiology
Yaqing Chen, Huanchan Zhou, Yushan Lai, Qi Chen, Xiao-Qiang Yu, Xiaoyun Wang
Summary: Insect gut microbiota plays crucial roles in insects, and can be influenced by external factors such as food and antibiotics. This study revealed that antibiotic-induced dysbiosis of gut microbiota affects energy and metabolic homeostasis in Spodoptera frugiperda.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Cell Biology
Ruhao Zhuo, Menghui Xu, Xiaoyun Wang, Bin Zhou, Xin Wu, Vanessa Leone, Eugene B. Chang, Xiang Zhong
Summary: This article summarizes the regulatory mechanisms of m(6)A modification on viruses and commensal microbiota, highlights the roles of m(6)A methylation in the interaction of host and microbes, and discusses drugs development targeting m(6)A modification.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2022)
Article
Entomology
Luoluo Wang, Zhichang Pang, Qi Chen, Zhentao Song, Yi Lu, Meng Yang, Jia Huang, Xiao-Qiang Yu, Xiaoyun Wang
Summary: This study analyzed the sublethal exposure of the bioinsecticide spinetoram to Aedes aegypti larvae and its effects on adult performance and susceptibility to dengue virus infection. The surviving adult mosquitoes exhibited smaller size and weaker blood-feeding capacity, as well as transgenerational sublethal effects on offspring survival rates. Additionally, surviving adult females had higher viral loads of dengue virus after spinetoram exposure. Mechanistically, inhibition of oxidative phosphorylation may stimulate dengue virus production in adult Ae. aegypti.
Article
Immunology
Luoluo Wang, Jian Wu, Runzhou Liu, Wenjun Chen, Zhichang Pang, Fan Zhou, Lu Xia, Jia Huang, Tao Pan, Xin-zhuan Su, Xiaoyun Wang
Summary: Malaria parasite infection significantly alters m(6)A mRNA modification and gene expression in the host spleen, and reprograms host immune response pathways by regulating m(6)A modification enzymes. This study represents the first characterization of host spleen m(6)A methylome triggered by malaria parasite infections, highlighting the importance of m(6)A modifications in host-parasite interactions.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Entomology
Yaqing Chen, Yushan Lai, Runzhou Liu, Lin Yao, Xiao-Qiang Yu, Xiaoyun Wang
Summary: In this study, the role of RNA m(6)A epigenetic regulation in the embryonic development of Spodoptera frugiperda was analyzed. The highly conserved function of m(6)A methyltransferases SfrMETTL3 and SfrMETTL14 among insects and mammals was discovered. Transcriptome-wide analysis revealed differential expression of m(6)A-modified transcripts in 2-hour and 24-hour embryos, with enrichment in genes related to cell and organ development. Moreover, it was found that RNA m(6)A methylation may regulate the transcriptional levels of genes related to tissue and organ development during the embryonic stage. This study provides new insights into the embryonic development of insects.
Article
Computer Science, Artificial Intelligence
Tian Tian, Ji Wan, Qi Song, Zhi Wei
NATURE MACHINE INTELLIGENCE
(2019)
Article
Multidisciplinary Sciences
Ji Wan, Xiangwei Gao, Yuanhui Mao, Xingqian Zhang, Shu-Bing Qian