Article
Biochemistry & Molecular Biology
Alec C. Gleason, Ghanashyam Ghadge, Yoshifumi Sonobe, Raymond P. Roos
Summary: Ribosome profiling and mass spectroscopy have identified noncanonical translation initiation codons (TICs) that translate oncogenic proteins. These TICs have flanking nucleotides closely matching the Kozak sequence, and cancer-associated genes have longer 5'UTRs, increasing the likelihood of ribosome binding to noncanonical TICs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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.
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)
Review
Biochemistry & Molecular Biology
Joanna R. Kovalski, Duygu Kuzuoglu-Ozturk, Davide Ruggero
Summary: This review discusses how cancer cells regulate protein expression through translational control and highlights the clinical potential of targeting translation factors as anti-cancer therapies. It also details the interaction between RNA sequence and structural elements, the translational machinery, and RNA-binding proteins in coordinating specific pro-survival and pro-growth programs. Additionally, the review provides an overview of current and emerging technologies for studying selective translational control in cancer cells and the tumor microenvironment.
Review
Cell Biology
Akira Fukao, Takumi Tomohiro, Toshinobu Fujiwara
Summary: Protein synthesis is tightly regulated at each step, with the formation of the eIF4F complex on the 5' cap structure of mRNA being a rate-limiting step. Various cis-elements on mRNA contribute to fine-tune protein expression, recognized and bound by trans-acting factors for regulating translation rate or mRNA stability. This review focuses on the regulation of the eIF4F complex assembly and translation initiation by trans-acting factors through cis-elements on mRNAs.
Article
Multidisciplinary Sciences
Alec C. Gleason, Ghanashyam Ghadge, Jin Chen, Yoshifumi Sonobe, Raymond P. Roos
Summary: This study improves the accuracy and prediction capability of identifying translation initiation sites in genes associated with neurologic repeat expansion disorders by optimizing feature selection, data sampling, and machine learning algorithms.
Article
Multidisciplinary Sciences
Leiming Dong, Yuanhui Mao, Aidong Zhou, Xiao-Min Liu, Jun Zhou, Ji Wan, Shu-Bing Qian
Summary: The study reveals that oncogenic signaling relaxes initiation pausing to increase translational flux, and mRNA m(6)A modification near start codons influences the behavior of initiating ribosomes, with reduced mRNA methylation promoting tumor growth.
Article
Biochemistry & Molecular Biology
Gustavo Barbosa de Lima, Thaise Yasmine Vasconcelos de Lima Cavalcanti, Adriana Neuman Albuquerque Lins Moura de Brito, Ludmilla Arruda de Assis, Rafaela Paiva Andrade-Vieira, Eden Ribeiro Freire, Tatiana Reichert da Silva Assuncao, Christian Robson de Souza Reis, Nilson Ivo Tonin Zanchin, Beatriz Gomes Guimaraes, Osvaldo Pompilio de-Melo-Neto
Summary: This study investigated the interacting proteins of Leishmania EIF4E5, revealing its main interaction with EIF4G1 and other proteins. The study also explored the interactions of EIF4E5's C-terminal end and protein partners.
Review
Immunology
Julia M. Marchingo, Doreen A. Cantrell
Summary: T cell activation and proliferation lead to significant changes in cell size and molecular content, resulting in an increased demand for energy and amino acids. Protein synthesis, a highly energy- and resource-demanding process, is closely linked to T cell energy production and proteome remodeling. The use of high-resolution mass spectrometry to analyze T cell proteomes can enhance our understanding of the regulation of these processes.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
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
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)
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
Biochemistry & Molecular Biology
Shijie Ma, Zizheng Dong, Yanfei Huang, Jing-Yuan Liu, Jian-Ting Zhang
Summary: In this study, we demonstrate that eIF3a controls cancer cell proliferation by regulating glucose metabolism through the activation of AMPK alpha via the phosphorylation at Thr(172) in its kinase activation loop. Our findings suggest a novel eIF3a-Rheb-AMPK signaling axis that translationally regulates glucose metabolism and proliferation in cancer cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Zhen Lin, Yuan Li, Yubei Wang, Xiaolei Liu, Liang Ma, Zhengjing Zhang, Chen Mu, Yan Zhang, Li Peng, Shaojun Xie, Chun-Peng Song, Huazhong Shi, Jian-Kang Zhu, Pengcheng Wang
Summary: Studies have shown that in plant responses to ABA signaling, the activity of SnRK2 kinase is rapidly activated through phosphorylation mediated primarily by B2 and B3 RAFs, with transphosphorylation between SnRK2s amplifying the signal transduction response.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Tea Lenarcic, Moritz Niemann, David J. F. Ramrath, Salvatore Calderaro, Timo Fluegel, Martin Saurer, Marc Leibundgut, Daniel Boehringer, Celine Prange, Elke K. Horn, Andre Schneider, Nenad Ban
Summary: This study investigates the assembly of the mitochondrial small subunit (mt-SSU) and identifies several assembly factors that interact with specific regions of rRNA to ensure proper assembly. The researchers use cryoelectron microscopy to determine the structures of assembly intermediates and propose a stepwise assembly process involving ribosomal protein and assembly factor exchange.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)