Review
Biochemistry & Molecular Biology
Rita Marques, Rafaela Lacerda, Luisa Romao
Summary: RNA-based therapies targeting IRESs and ITAFs have shown potential benefits in various conditions. IRES-mediated translation is an alternative mechanism that helps maintain protein synthesis and is involved in stress response and disease development. The relationship between IRESs, ITAFs, tumorigenesis, and therapy resistance has been studied, providing new therapeutic targets and approaches. In addition, dysregulation of IRES-dependent translation initiation is also associated with neurological and cardiovascular diseases, muscular atrophies, and other syndromes.
Review
Virology
Brenda Lopez-Ulloa, Yazmin Fuentes, Magdalena S. Pizarro-Ortega, Marcelo Lopez-Lastra
Summary: In this review, we discuss vRNA IRES-mediated translation initiation, highlighting the role of RNA-binding proteins (RBPs), other than the canonical translation initiation factors, in regulating their activity.
Article
Biochemistry & Molecular Biology
Wataru Nishima, Dylan Girodat, Mikael Holm, Emily J. Rundlet, Jose L. Alejo, Kara Fischer, Scott C. Blanchard, Karissa Y. Sanbonmatsu
Summary: This study combines molecular simulations with single-molecule fluorescence resonance energy transfer imaging to uncover the key steps of ribosome completion and resetting during translocation. Diffusive motions of the ribosomal small subunit head domain and the role of ribosomal RNA enable mRNA and tRNA to achieve full translocation, while the engagement of peptidyl-tRNA and disengagement of deacyl-tRNA facilitate the ribosome resetting mechanism.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ze Liu, Justin Wang, Yi Shi, Brian A. Yee, Markus Terrey, Qian Zhang, Jenq-Chang Lee, Kuo- Lin, Andrew H-J Wang, Susan L. Ackerman, Gene W. Yeo, Haissi Cui, Xiang-Lei Yang
Summary: Translational readthrough of UGA stop codons by selenocysteine-specific tRNA enables the synthesis of selenoproteins. In addition, this mechanism can also increase translational readthrough of non-selenocysteine genes to create C-terminally extended isoforms. The recognition of target mRNAs by seryl-tRNA synthetase is dependent on its enzymatic activity and a vertebrate-specific domain. The findings expand our understanding of selenoprotein biosynthesis and suggest a potential avenue for therapeutic targeting of nonsense mutations using endogenous factors.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Carol Dalgarno, Kristen Scopino, Mitsu Raval, Clara Nachmanoff, Eric D. Sakkas, Daniel Krizanc, Kelly M. Thayer, Michael P. Weir
Summary: The ribosome CAR interaction surface extends the decoding center A site and interacts with the next +1 codon through H-bonds. Molecular dynamic simulations reveal codon sequence specificity of the CAR-mRNA interaction, with a preference for GCN codons. Nucleotide substitution experiments show that the first nucleotide of the +1 codon dominates the CAR-mRNA interaction, and the CAR/+1 codon interaction is influenced by nucleotide 3 of +1 GCN codons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Evan M. Zhao, Angelo S. Mao, Helena de Puig, Kehan Zhang, Nathaniel D. Tippens, Xiao Tan, F. Ann Ran, Isaac Han, Peter Q. Nguyen, Emma J. Chory, Tiffany Y. Hua, Pradeep Ramesh, David B. Thompson, Crystal Yuri Oh, Eric S. Zigon, Max A. English, James J. Collins
Summary: The use of eukaryotic toehold switches (eToeholds) allows for efficient induction of gene translation in eukaryotic cells, capable of distinguishing the presence of RNA transcripts under various circumstances. Through optimization of RNA annealing, up to 16-fold induction of transgene expression was achieved.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ofri Levi, Yoav S. Arava
Summary: The study identified a novel integrated pathway where Pus6 'writes' modifications on tRNA and mRNA, and both types of RNAs are 'read' by MetRS for translation regulation purposes.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Hai-Bo Xiong, Hui-Min Pan, Qiao-Ying Long, Zi-Yuan Wang, Wan-Tong Qu, Tong Mei, Nan Zhang, Xiao-Feng Xu, Zhong-Nan Yang, Qing-Bo Yu
Summary: This study reveals the mechanism of transcription-translation coupling in chloroplasts and finds that AtNusG-mediated coupling contributes to the establishment of photosynthetic capacity and response to environmental changes in plants.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Bingyi Chen, Siting Luo, Songxuan Zhang, Yingchen Ju, Qiong Gu, Jun Xu, Xiang-Lei Yang, Huihao Zhou
Summary: Reveromycin A (RM-A) selectively inhibits eukaryotic cytoplasmic isoleucyltRNA synthetase (IleRS). The co-crystal structure suggests that RM-A molecule occupies the tRNA(Ile) binding site of Saccharomyces cerevisiae IleRS, and that RM-A cooperates with isoleucine or isoleucyl-adenylate for IleRS binding.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Elin Strand, Hanne Hollas, Siri Aastedatter Sakya, Sofya Romanyuk, Mikko E. Saraste, Ann Kari Grindheim, Sudarshan S. Patil, Anni Vedeler
Summary: AnxA2 regulates c-Myc expression by binding to c-myc mRNA and possibly silencing it during transport, while acting as a switch to turn off c-Myc IRES activity in the presence of calcium.
Article
Microbiology
Yu-Siang Su, Lih-Hwa Hwang, Chi-Ju Chen
Summary: The study demonstrated the integral role of HSPA6 in EV-A71 infection as a positive regulator, showcasing its impact on viral protein production and virion assembly, specifically through the regulation of IRES-mediated translation.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemical Research Methods
Mengyan Zhang, Maciej Bartosz Holowko, Huw Hayman Zumpe, Cheng Soon Ong
Summary: This study proposes a machine learning guided Design-Build-Test-Learn (DBTL) cycle for the experimental design of bacterial ribosome binding sites (RBSs). By integrating machine learning algorithms with laboratory automation and high-throughput processes, the researchers were able to reliably design small genetic parts with high translation initiation rates.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Virology
Mathew P. Kirby, Ciara Stevenson, Liam J. Worrall, Yihang Chen, Christina Young, Jisoo Youm, Natalie C. J. Strynadka, Douglas W. Allan, Eric Jan
Summary: Viruses rely on internal ribosome entry sites to utilize the host cell machinery for viral protein expression. Mutations in the hinge region of dicistrovirus IRES revealed its significant role in viral translation.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zhicong Zhao, Ying Qing, Lei Dong, Li Han, Dong Wu, Yangchan Li, Wei Li, Jianhuang Xue, Keren Zhou, Miao Sun, Brandon Tan, Zhenhua Chen, Chao Shen, Lei Gao, Andrew Small, Kitty Wang, Keith Leung, Zheng Zhang, Xi Qin, Xiaolan Deng, Qiang Xia, Rui Su, Jianjun Chen
Summary: The mRNA internal m7G modification is recognized by Quaking proteins (QKIs), which regulate mRNA stability and translation, affecting cellular drug resistance.
Article
Biochemistry & Molecular Biology
Anna Miscicka, Kristen Lu, Irina S. Abaeva, Tatyana V. Pestova, Christopher U. T. Hellen
Summary: Translation initiation on viral mRNAs can occur through noncanonical mechanisms involving ribosome binding to an internal ribosome entry site (IRES). Dicistroviruses, such as cricket paralysis virus (CrPV), have long IRESs that initiate translation without conventional initiation factors. Recent discoveries have identified shorter IRESs in dicistrovirus-like genomes, like nedicistrovirus (NediV) and Antarctic picorna-like virus 1 (APLV1), which initiate translation from non-AUG codons. These NediV-like IRESs bind directly to the ribosomal peptidyl (P) site and form functional ribosomal complexes without initiation factors.
