Review
Genetics & Heredity
Prakash Amruth Raj Chukka, Stacey D. Wetmore, Nehal Thakor
Summary: Translational control plays a crucial role in dictating gene expression and altering physiological processes in eukaryotic cells. eIF5B plays a significant role in this process, especially in the survival and drug resistance of cancer cells.
FRONTIERS IN GENETICS
(2021)
Review
Cell Biology
Yudi Liu, Jiuwei Cui, Andrew R. Hoffman, Ji-Fan Hu
Summary: Protein translation is a critical regulatory event involved in various physiological and pathological processes. The eukaryotic translation initiation factor 4G2 (eIF4G2) is important for cap-independent translation initiation via internal ribosome entry sites (IRESs), but recent findings suggest that it plays a role in other translation initiation pathways as well. This review summarizes the role of eIF4G2 in different translation initiation events and its involvement in apoptosis, cell survival, cell differentiation, and embryonic development.
CELL PROLIFERATION
(2023)
Article
Biochemistry & Molecular Biology
Zuben P. Brown, Irina S. Abaeva, Swastik De, Christopher U. T. Hellen, Tatyana Pestova, Joachim Frank
Summary: This study presents cryo-EM structures of hepatitis C virus IRES initiation complexes, revealing the dynamic network of 40S/IRES contacts and the conformational changes during the transition from eIF2- to eIF5B-containing 48S complexes, providing important insights into the process of subunit joining.
Article
Biochemistry & Molecular Biology
Patrick Senechal, Francis Robert, Regina Cencic, Akiko Yanagiya, Jennifer Chu, Nahum Sonenberg, Marilene Paquet, Jerry Pelletier
Summary: The translation initiation factor eIF4F is crucial for cap-dependent protein synthesis initiation. Different subunits of eIF4F have varying roles in development and tumorigenesis, with some being essential for viability and tumor onset, while others have non-essential functions. This study highlights the complex roles of different eIF4F subunits in gene expression regulation during embryogenesis and tumor development.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Emma Minnee, William James Faller
Summary: Protein synthesis is crucial in all kingdoms of life, and dysregulation can drive cancer development, as seen in colorectal cancer with translational reprogramming. Multiple signaling pathways impact the translation initiation machinery, playing a critical role in regulating gene expression differentially.
Article
Biochemistry & Molecular Biology
Jack D. Godfrey, Daniel Hejazi, Xiaofei Du, Cenfu Wei, Eshaan Rao, Christopher M. Gomez
Summary: The HER2/neu signaling pathway is frequently mutated in human cancer and targeting this pathway is effective in treatment. However, cancer cells often develop resistance. This study shows that smaller c-terminal fragments (CTFs) of the HER2 protein, generated through internal translation, are a cause of resistance. Understanding this mechanism could lead to new therapeutic interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Paul Powell, Usha Bhardwaj, Dixie Goss
Summary: This study identifies secondary structures that selectively interact with eIF3 and explores its role in translation initiation of BYDV. The findings propose a new model for BYDV translation initiation and expand the known functionality of eIF3.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Oncology
Chengzhi Xu, Yupeng Shen, Yong Shi, Ming Zhang, Liang Zhou
Summary: This study reveals the role of EIF3B in head and neck squamous cell carcinoma (HNSCC) and identifies its promotion of CEBPB translation and IL6R expression. These findings provide important insights into the molecular basis and pathogenesis of HNSCC.
CANCER CELL INTERNATIONAL
(2022)
Article
Multidisciplinary Sciences
Christina Akirtava, Gemma E. May, C. Joel McManus
Summary: The study found that the putative IRESes previously reported in Hox gene hTLs are rarely included in transcript leaders and instead function independently as transcriptional promoters. Additionally, the proposed RNA structure of the putative Hoxa9 IRES is not conserved. The majority of hTLs with putative IRES activity overlap with transcriptional promoters, enhancers, and 3' splice sites, arguing against widespread IRES-like activities from hTLs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Virology
Shichong Han, Xiaojia Wang, Junyong Guan, Jinen Wu, Yun Zhang, Pinghua Li, Zaixin Liu, Sahibzada Waheed Abdullah, Zhihui Zhang, Ye Jin, Shiqi Sun, Huichen Guo
Summary: Nucleolin (NCL) is identified as a protein interacting with foot-and-mouth disease virus (FMDV) IRES and regulating translation of various IRES-containing viruses. NCL plays a substantial role in viral replication by directly regulating viral protein production and indirectly influencing FMDV RNA synthesis. The cytoplasmic relocalization of NCL during FMDV infection is crucial for viral IRES-driven translation, highlighting its importance as a potential target for antiviral interventions.
JOURNAL OF VIROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jerry Pelletier, Nahum Sonenberg
Summary: Fundamental studies have elucidated the role of eukaryotic initiation factor (eIF) 4E in mRNA translation and its regulation. The regulation of translation by eIF4E is crucial for cellular homeostasis under normal conditions. In response to stress, eIF4E processes gene flow information to support adaptive mechanisms for cell survival. Dysregulated eIF4E activity contributes to tumor development, progression, and therapy response modulation. Therefore, there is a growing interest in understanding eIF4E function in gene expression control and developing strategies to inhibit its activity for disease treatment.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Su Wu, Gerhard Wagner
Summary: eIF4F plays diverse roles in human cancers, with overexpression of EIF4G1 being more selective than EIF4E, serving as a prognostic indicator in cancer patients. This expression imbalance affects housekeeping pathways and cancer-related pathways, leading to cap-independent initiation due to eIF4G1 hyperphosphorylation. These findings provide a novel model of dysregulated eIF4F function and highlight the clinical relevance of cap-(in)dependent initiation in cancer.
Article
Biochemistry & Molecular Biology
Xiaozhuo Liu, Houtan Moshiri, Qian He, Ansuman Sahoo, Sarah E. Walker
Summary: The yeast eukaryotic initiation factor 4B plays an important role in translation preinitiation complexes. Recent studies have found that yeast mRNAs have differential dependence on eIF4B under different growth conditions. It is suggested that the activity of eIF4B in translation may alter yeast phenotypes by selecting different mRNAs. By comparing the effects of disrupting yeast eIF4B RNA- and 40S-binding motifs, it is found that the 40S-binding N-terminal Domain (NTD) is associated with stress responses and promotes yeast growth. Deletion of the NTD significantly reduces translation activity and alters the composition of ribosome-associated mRNAs. Gene ontology analysis reveals that transcripts dependent on the NTD encode proteins associated with the cellular membrane system and the cell wall.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Developmental Biology
Yan Li, Jianan Tang, Xu Ji, Min-Min Hua, Miao Liu, Lu Chang, Yihua Gu, Changgen Shi, Wuhua Ni, Jing Liu, Hui-juan Shi, Xuefeng Huang, Christopher O'Neill, Xingliang Jin
Summary: The translation initiation factor eIF4E plays a crucial role in cap-dependent translation and the transition from maternal to embryonic control of mouse embryo development. Inhibiting eIF4E activity leads to developmental arrest at the two-cell stage, highlighting the importance of eIF4E in early embryonic transitions. This study also shows that mTOR activity and the negative regulator 4E-BP1 are involved in regulating eIF4E activity during embryonic development.
Article
Chemistry, Medicinal
Xintao Gao, Yonglong Jin, Wenyong Zhu, Xiaochen Wu, Jing Wang, Chuanlong Guo
Summary: eIF4E is a central regulator in cancer cell growth, but there are currently no clinically available eIF4E inhibitors. Interfering with eIF4E/eIF4G interactions may provide a new strategy for designing eIF4E inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Anton A. Komar, William C. Merrick
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemical Research Methods
David Holcomb, Aikaterini Alexaki, Nancy Hernandez, Ryan Hunt, Kyle Laurie, Jacob Kames, Nobuko Hamasaki-Katagiri, Anton A. Komar, Michael DiCuccio, Chava Kimchi-Sarfaty
Summary: The study found that certain human proteins interact with SARS virus proteins, potentially influencing the severity of COVID-19. The computational analysis of these interactions sheds light on the impact of genetic variants of these proteins on disease severity. Further investigation is needed to better understand the pathogenesis of COVID-19, especially in minority groups.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Anton A. Komar
Summary: The genetic code establishes the relationship between nucleotide triplets in mRNA and amino acids during protein synthesis, with most amino acids being encoded by multiple synonymous codons. The specific choice of codons may have functional implications beyond coding for amino acids, and strategic placement of synonymous codons in mRNA impacts translation dynamics and co-translational protein folding in the cell.
BIOCHEMISTRY-MOSCOW
(2021)
Article
Developmental Biology
Evelyn Llerena Cari, Synneva Hagen-Lillevik, Asma Giornazi, Miriam Post, Anton A. Komar, Leslie Appiah, Benjamin Bitler, Alex J. Polotsky, Nanette Santoro, Jeffrey Kieft, Kent Lai, Joshua Johnson
Summary: The mechanisms controlling mammalian ovarian primordial follicle growth activation and selection for survival are largely unknown. Research has shown that normal ovarian cells express stress response markers, indicating a potential role in follicle growth activation and survival regulation. Translation regulation may play a key role in determining the pace of follicle growth and the response to cellular stress or damage, ultimately impacting DNA repair and genomic integrity.
MOLECULAR HUMAN REPRODUCTION
(2021)
Article
Genetics & Heredity
Douglas Meyer, Jacob Kames, Haim Bar, Anton A. Komar, Aikaterini Alexaki, Juan Ibla, Ryan C. Hunt, Luis Santana-Quintero, Anton Golikov, Michael DiCuccio, Chava Kimchi-Sarfaty
Summary: This study analyzed the changes in codon usage in cancer patients based on gene expression variability across tissues, identifying distinct patterns of codon preference changes for different cancer types affecting the same tissue. Furthermore, the research revealed an association between differences in codon usage between healthy and tumor tissue and patient survival rates. The development of the CancerCoCoPUTs database provides a comprehensive resource for codon-usage-oriented cancer research.
Article
Biochemistry & Molecular Biology
Richard Anderson, Anchal Agarwal, Arnab Ghosh, Bo-Jhih Guan, Jackson Casteel, Nina Dvorina, William M. Baldwin, Barsanjit Mazumder, Taras Y. Nazarko, William C. Merrick, David A. Buchner, Maria Hatzoglou, Roman Kondratov, Anton A. Komar
Summary: eIF2A plays a crucial role in cellular development and stress response, and its knockout results in reduced lifespan, disrupted lipid homeostasis, decreased abundance of immune cells, and potentially affects sex-specific pathways. The identification of eIF2A function in the development of metabolic syndrome holds promise for further insights into specific eIF2A targets responsible for these changes.
Article
Cell Biology
Anton A. Komar
Summary: Protein folding in the cell is largely co-translational, occurring during protein synthesis on the ribosome. It has been found that co-translational folding is characteristic of almost all types of proteins in the cell, including single and multidomain, single and multisubunit, cytosolic, secretory, and membrane proteins. However, many details of co-translational folding are still not fully understood. Recent research has shown that folding of a beta-barrel protein begins with the formation of an alpha-helix inside the ribosome, which then rearranges into a beta-hairpin structure as the peptide grows and reaches the wider region of the ribosomal exit tunnel.
Article
Multidisciplinary Sciences
Kepeng Che, Ajaybabu Pobbati, Caleb N. Seavey, Yuriy Fedorov, Anton A. Komar, Ashley Burtscher, Shuang Ma, Brian P. Rubin
Summary: In this study, the researchers identified a pharmacologically active small molecule called aurintricarboxylic acid (ATA) that can disrupt the formation of the TAZ-TEAD complex. They found that ATA inhibits TC/TEAD transcriptional activity and prevents anchorage-independent growth associated with dysregulated TAZ/TEAD activity.
Article
Hematology
Upendra K. Katneni, Aikaterini Alexaki, Ryan C. Hunt, Nobuko Hamasaki-Katagiri, Gaya K. Hettiarachchi, Jacob M. Kames, Joseph R. McGill, David D. Holcomb, John C. Athey, Brian Lin, Leonid A. Parunov, Tal Kafri, Qi Lu, Robert Peters, Mikhail V. Ovanesov, Daron I. Freedberg, Haim Bar, Anton A. Komar, Zuben E. Sauna, Chava Kimchi-Sarfaty
Summary: In this study, we evaluated the effects of gene recoding on F9 protein and found that it can alter protein conformation, translation kinetics, and immunogenicity. Moreover, posttranslational modifications were also influenced by gene recoding. These findings have general applicability and implications for other gene-recoded recombinant proteins.
Article
Hematology
Reem Elagooz, Anita R. Dhara, Rose M. Gott, Sarah E. Adams, Rachael A. White, Arnab Ghosh, Shinjini Ganguly, Yuncheng Man, Amma Owusu-Ansah, Omar Y. Mian, Umut A. Gurkan, Anton A. Komar, Mahesh Ramamoorthy, Merlin Nithya Gnanapragasam
Summary: The switching of fetal-to-adult hemoglobin involves the regulation of certain proteins in red blood cells. In this study, researchers identified PUM1, an RNA-binding protein, as a regulator of this process by affecting the stability and translation efficiency of certain genes. Silencing PUM1 increased the expression of fetal hemoglobin, providing a new strategy for treating certain hemoglobin disorders.
Review
Biochemistry & Molecular Biology
Anton A. Komar
Summary: The study of peptides has helped understand the relationship between protein structure and activity. Short peptides can be used as therapeutic agents, but often have lower activity due to reduced structural organization, stability, and solubility. Various approaches, such as molecular stapling and peptide grafting, have been developed to improve the biological activity of short peptides by enforcing a more stable and active conformation.
Article
Virology
Sarah E. Fumagalli, Nigam H. Padhiar, Douglas Meyer, Upendra Katneni, Haim Bar, Michael DiCuccio, Anton A. Komar, Chava Kimchi-Sarfaty
Summary: This study analyzed the nucleotide and synonymous codon usage features, as well as mutation patterns of SARS-CoV-2. It found a higher proportion of synonymous mutations in specific positions, but a higher number of nonsynonymous mutations compared to other RNA viruses. The usage patterns of nucleotides and codons remained relatively consistent over the 32-month period, but the CAI and dN/dS values varied significantly between different timepoints and genes.
Article
Biochemical Research Methods
David D. Holcomb, Katarzyna I. Jankowska, Nancy Hernandez, Kyle Laurie, Jacob Kames, Nobuko Hamasaki-Katagiri, Anton A. Komar, Michael Dicuccio, Chava Kimchi-Sarfaty
Summary: This study describes a bioinformatics pipeline that evaluates the interactions between coagulation-related proteins and SARS-CoV-2 proteins, and predicts the disease pathogenesis in specific subpopulations.
Article
Virology
Abhijit Basu, Srinivasa Penumutchu, Kien Nguyen, Uri Mbonye, Blanton S. Tolbert, Jonathan Karn, Anton A. Komar, Barsanjit Mazumder
Summary: This study identifies two novel cis-regulatory elements in the SARS-CoV-2 genome and describes their role in translational control. These elements interact with a signaling pathway involving DAP-kinase1, leading to the release of ribosomal protein L13a and translational silencing. The conservation of these elements suggests their importance for SARS-CoV-2.
JOURNAL OF VIROLOGY
(2022)
Article
Biology
Brandon Trainor, Anton Komar, Dimitri Pestov, Natalia Shcherbik
Summary: This article provides a simple, fast, and cost-effective method for extracting translationally active cell-free extract (CFE) from yeast, and describes techniques for validating and troubleshooting the quality and translational activity of the obtained yeast CFE.
