Article
Multidisciplinary Sciences
Chie Kikutake, Mikita Suyama
Summary: Recent studies have shown that some silent mutations can be harmful to cancer pathogenesis. In this study, a comprehensive in silico analysis was performed using exome sequencing data from the Cancer Genome Atlas to investigate the effects of silent mutations on cancer development. The study found that later-occurring mutations had higher codon optimality scores compared to earlier-occurring mutations. High-score mutations were enriched in genes involved in cell cycle and division, while low-score mutations were enriched in genes involved in apoptosis and cellular senescence. These findings indicate that silent mutations can play a role in cancer pathogenesis.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Sayanur Rahaman, Simone Faravelli, Sylvia Voegeli, Attila Becskei
Summary: The stability gain of mRNA in yeast depends on the mRNA coding sequence length. Codon optimality affects mRNA stability and polysome propensity above a threshold length. The untranslated regions (UTR) can tune this threshold length and some UTRs can destabilize mRNAs without reducing translation, which is important for controlling the oscillatory expression of cell cycle genes.
Article
Biochemistry & Molecular Biology
Goro Terai, Kiyoshi Asai
Summary: This paper proposes a method for extracting secondary structure features that affect the functional activity of RNA from sequence-activity data. The method is applied to different experimental systems and provides detailed insights into the structure-activity relationships of RNA.
NUCLEIC ACIDS RESEARCH
(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)
Review
Biochemistry & Molecular Biology
Fabian Hia, Osamu Takeuchi
Summary: The central dogma of molecular biology states that genetic information is transferred from nucleic acid to proteins. Recent research has highlighted the importance of mRNA regulation in controlling protein abundances, with a specific focus on codon bias and optimality. This system allows different organisms or cell types to coordinate physiological pathways in response to various stress or growth conditions.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Marion A. L. Picard, Fiona Leblay, Cecile Cassan, Anouk Willemsen, Josquin Daron, Frederique Bauffe, Mathilde Decourcelle, Antonin Demange, Ignacio G. Bravo
Summary: Differences in codon frequency have significant effects on transcription and translation efficiency, leading to phenotypic and functional differences. This study presents a multiscale analysis of synonymous codon recoding effects during heterologous gene expression and quantifies the impact of codon usage bias at different molecular and cellular levels. The results demonstrate that codon usage bias strongly influences molecular and cellular phenotype, affecting mRNA and protein levels, leading to reproducible phenotypic heterogeneity and trade-off between antibiotic resistance and heterologous expression burden. In human cells, codon usage bias modulates gene expression by altering mRNA availability and suitability for translation, resulting in protein level differences and functional phenotypic changes.
Article
Multidisciplinary Sciences
Dominic Simm, Blagovesta Popova, Gerhard H. Braus, Stephan Waack, Martin Kollmar
Summary: The study analyzed the influence of a profiled codon usage adaptation approach on protein expression levels in the eukaryotic model organism Saccharomyces cerevisiae. Results showed that high levels of GFP expression and adaptation of toxic α Syn to endogenous low-level expression could be achieved using this approach. The new software for performing host-specific protein adaptations to commonly used model organisms is publicly available as a web-application.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Fengbiao Zhou, Nesrine Aroua, Yi Liu, Christian Rohde, Jingdong Cheng, Anna-Katharina Wirth, Daria Fijalkowska, Stefanie Goellner, Michelle Lotze, Haiyang Yun, Xiaobing Yu, Caroline Pabst, Tim Sauer, Thomas Oellerich, Hubert Serve, Christoph Roellig, Martin Bornhaeuser, Christian Thiede, Claudia Baldus, Michaela Frye, Simon Raffel, Jeroen Krijgsveld, Irmela Jeremias, Roland Beckmann, Andreas Trumpp, Carsten Mueller-Tidow
Summary: The dynamic 2'-O-methylation of ribosomal RNA regulates leukemia stem cell activity in acute myeloid leukemia. The methylation pattern is associated with AML development stage and stem cell gene expression. Enhanced 2'-O-methylation redirects ribosome translation and controls AML stem cell self-renewal.
Article
Biochemistry & Molecular Biology
Janaina Lima de Oliveira, Atahualpa Castillo Morales, Laurence D. Hurst, Araxi O. Urrutia, Christopher R. L. Thompson, Jason B. Wolf
Summary: Studies have found that synonymous codons are used at different frequencies due to the effects of neutral and selective forces. Selection in highly expressed genes remains to be extensively studied, with some evidence suggesting that certain factors do not impact codon preference.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Review
Biochemistry & Molecular Biology
Shir Bahiri-Elitzur, Tamir Tuller
Summary: Codon usage bias refers to the differing frequencies of synonymous codons in genes and organisms, believed to be a balance between mutational biases and natural selection. Various codon usage bias indices have been developed to estimate the fitness of coding sequences to different phenomena, with applications in biomedical fields. Despite the differences in aims, many indices tend to correlate, highlighting the importance of continuously developing new indices to capture additional aspects of gene expression steps.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Ping Song, Fan Yang, Hongchuan Jin, Xian Wang
Summary: In addition to gene regulation and post-translational modifications, abnormal translation from mRNAs to proteins is essential in cancer pathogenesis. Targeting mRNA translation presents a potential strategy for cancer treatment. Modulation of protein translation involves factors such as initiation factors, RNA-binding proteins, mRNA modifications like m(6)A, and noncoding RNAs like microRNAs and long noncoding RNAs. This review highlights the interplay between mRNA modifications and ncRNAs in regulating protein translation, offering insights for precision therapy in human cancers.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Biochemical Research Methods
Francesco Bardozzo, Pietro Lio, Roberto Tagliaferri
Summary: Studying the oscillations of biomolecules at different levels of application can reveal insights into the underlying mechanisms of living cells. Integrating network/pathway-level information with genetic information allows for a description of bacterial mechanisms and organism-specific dynamics.
Review
Pharmacology & Pharmacy
Brian C. Lin, Nayiri M. Kaissarian, Chava Kimchi-Sarfaty
Summary: Synonymous gene recoding, a method to substitute synonymous variants into genetic sequence, has been used to overcome production limitations in therapeutic development. However, evaluating the safety and efficacy of recoded therapeutics is challenging due to subtle but impactful changes in protein features caused by synonymous codon substitutions, requiring sensitive detection methods.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
William Gao, Carlos J. Gallardo-Dodd, Claudia Kutter
Summary: This study examines the correlation between codon and anticodon pools and their impact on translation efficiency at the individual cell level. The researchers found that codon usage and amino acid demand are highly stable across different cell types. They also discovered a strong correlation between amino acid supply and demand in almost all cell types. Notably, neurons showed enhanced translation efficiency due to an increased supply of specific tRNA anticodons. This study provides valuable insights into translation elongation in mammalian cells and suggests potential implications for neurological pathologies.
Review
Biochemistry & Molecular Biology
Qiushuang Wu, Ariel A. Bazzini
Summary: Messenger RNA (mRNA) stability and translational efficiency play crucial roles in protein production. Recent studies have shown that ribosomes, in addition to protein synthesis, also control mRNA stability in a codon-dependent manner known as codon optimality. Codons have a significant impact on mRNA stability and provide cis-regulatory information beyond their encoding amino acids. The molecular mechanism of codon optimality is still not fully understood, but it appears that the translation elongation rate triggers mRNA decay, where transfer RNAs may serve as master gene regulators influencing mRNA stability. This article discusses the findings of codon optimality and gene regulation related to codon composition in different eukaryotic species.
ANNUAL REVIEW OF BIOCHEMISTRY
(2023)
Article
Biochemical Research Methods
Maya Galili, Tamir Tuller
BMC BIOINFORMATICS
(2020)
Article
Genetics & Heredity
Yoram Zarai, Zohar Zafrir, Bunpote Siridechadilok, Amporn Suphatrakul, Modi Roopin, Justin Julander, Tamir Tuller
Review
Biochemistry & Molecular Biology
Shir Bahiri-Elitzur, Tamir Tuller
BIOCHEMICAL SOCIETY TRANSACTIONS
(2020)
Article
Biochemical Research Methods
Doron Levin, Tamir Tuller
PLOS COMPUTATIONAL BIOLOGY
(2020)
Article
Genetics & Heredity
Tal Gutman, Guy Goren, Omri Efroni, Tamir Tuller
Summary: Silent mutations have significant predictive power over cancer classification and survival prognosis, likely due to their impact on gene expression. Combining both non-silent and silent mutations can achieve the best classification and survival estimation results for various cancer types. It is recommended to integrate silent mutations into cancer research to fully understand the genomic landscape of cancer and its implications on cancer fitness.
NPJ GENOMIC MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Tamar Neumann, Tamir Tuller
Summary: This study developed a predictive model of small subunit (SSU) density based on TCP-seq data and analyzed the effect of transcript features on SSU scanning dynamics. The results showed that the AUG context indeed affects the movement of the SSU, strong folding may cause the detachment of the SSU from the mRNA, and several novel sequence motifs can affect the SSU scan.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemical Research Methods
Itamar Menuhin-Gruman, Matan Arbel, Niv Amitay, Karin Sionov, Doron Naki, Itai Katzir, Omer Edgar, Shaked Bergman, Tamir Tuller
Summary: Modern synthetic biology relies on stable genetic constructs, but maintenance requires cell energy and natural selection can lead to loss of construct functionality. The ESO software tool automates the design of evolutionarily stable constructs while considering host organism characteristics to balance stability and gene expression.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Biochemical Research Methods
David Shallom, Danny Naiger, Shlomo Weiss, Tamir Tuller
Summary: In recent years, intracellular biophysical simulations have been increasingly used in both basic scientific research and synthetic biology. These simulations are time-consuming due to the complex networks of interactions between millions of components, and running them on parallel computers is not easy. This study presents a novel approach using dedicated hardware to address this issue, focusing specifically on simulating mRNA translation at a much faster rate than software solutions.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Biology
Liyam Chitayat Levi, Ido Rippin, Moran Ben Tulila, Rotem Galron, Tamir Tuller
Summary: The development of computational biology methodologies has provided a comprehensive understanding of the complexity of microbiomes and their impact on the environment. However, current microbiome engineering techniques neglect the interactions between genetic information and bacterial populations. In this study, a generic computational method was developed to automatically tune gene expression in microbiomes based on user preferences. The method has been validated through computational and experimental tools.
Article
Biotechnology & Applied Microbiology
Arup Panda, Tamir Tuller
Summary: The environment may impact the codon and amino acid choice of microbial communities, and samples from similar environmental niches show similar codon and amino acid distribution compared to samples from other habitats. Factors like GC content, functional or taxonomic abundance cannot fully explain the trends observed at the codon or amino acid level, implying a direct environmental influence on them.
NPJ BIOFILMS AND MICROBIOMES
(2023)
Review
Biotechnology & Applied Microbiology
Matan Arbel-Groissman, Itamar Menuhin-Gruman, Doron Naki, Shaked Bergman, Tamir Tuller
Summary: Evolutionary stability of synthetic constructs made of heterologous genes is a major challenge in synthetic biology, and the available tools to address this challenge are discussed in this review.
TRENDS IN BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Rami Katz, Elad Attias, Tamir Tuller, Michael Margaliot
Summary: Research has shown that mRNAs compete for shared resources during translation, which can significantly impact the global dynamics of translation in the cell when resources are scarce. By modeling this competition using a network approach, it was found that adding a new mRNA has a complex effect on total protein production, with diminishing marginal utility as the number of mRNAs increases, leading to saturation of total protein production rate to a limiting value.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2022)
Article
Biochemistry & Molecular Biology
Stav Carmel Ezra, Tamir Tuller
Summary: This study investigates the translation initiation process in chloroplasts and develops computational models to understand and model translation regulation. The folding energy of rRNA and mRNA is found to correlate with codon usage and protein levels. Additionally, the presence of various structural elements in chloroplast transcripts is reported.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Sophie Vinokour, Tamir Tuller
Summary: The study demonstrates the use of generic algorithms to introduce silent mutations for optimizing or reducing ribosomal traffic jams during mRNA translation. The cost of these algorithms includes factors such as computational time and the number of mutations introduced, enriching the methods for translation engineering.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Shir Bahiri-Elitzur, Tamir Tuller
Summary: Codon usage bias refers to the differing frequencies of synonymous codons in genes and organisms, believed to be a balance between mutational biases and natural selection. Various codon usage bias indices have been developed to estimate the fitness of coding sequences to different phenomena, with applications in biomedical fields. Despite the differences in aims, many indices tend to correlate, highlighting the importance of continuously developing new indices to capture additional aspects of gene expression steps.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)