Article
Virology
Xinying Wang, Marli Vlok, Stephane Flibotte, Eric Jan
Summary: The study explores a novel viral translational mechanism, uncovering the IGR IRES sequence from ancient Northwest territories cripavirus dating back 700 years. The research demonstrates that aNCV IRES can bind to ribosomes and drive translation, supporting the historical significance of this viral translational mechanism.
Article
Virology
Leandro Fernandez-Garcia, Jenniffer Angulo, Hade Ramos, Aldo Barrera, Karla Pino, Jorge Vera-Otarola, Marcelo Lopez-Lastra
Summary: The DENV IRES enables viral protein synthesis under conditions that suppress canonical translation initiation, with resistance to eIF4G cleavage and enhanced activity in HEK 293T cells expressing Human rhinovirus 2A protease. This study characterizes the mechanism dependent on an internal ribosome entry site (IRES) for DENV mRNA translation initiation both in vitro and in cells.
JOURNAL OF VIROLOGY
(2021)
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
Immunology
Guan-Hong Wu, Kuo-Ming Lee, Chia-Yu Kao, Shin-Ru Shih
Summary: The role of the internal ribosome entry site (IRES) in determining the neurovirulence of enteroviruses EV-A71 and CV-A16 was characterized using an oral inoculation model. Replacing EV-A71 IRES with CV-A16 abolished neuropathological phenotypes, indicating that IRES determines the neurotropic potential of these viruses. Tissue-specific replication can be reflected in cell-based characterization.
MICROBES AND INFECTION
(2023)
Article
Plant Sciences
Helena Jaramillo-Mesa, Emma Fischer, Aurelie M. Rakotondrafara
Summary: Diverse elements within the 5' untranslated region of mRNA can affect translation efficiency. This study reveals the cooperative role of multiple CU-rich segments flanking the TriMV YX-AUG motif in internal initiation of translation. These auxiliary domains may enhance ribosome capacity and delivery to the correct initiation site.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Multidisciplinary Sciences
Yan Zhang, Nikolay A. Aleksashin, Dorota Klepacki, Caleb Anderson, Nora Vazquez-Laslop, Carol A. Gross, Alexander S. Mankin
Summary: Kasugamycin (KSG) is a small ribosomal subunit-targeting antibiotic that interferes with translation in different stages. It inhibits protein synthesis by blocking the binding of canonical messenger RNA (mRNA) and initiator transfer RNA (tRNA) to the small ribosomal subunit. Even after the formation of the 70S initiation complex, KSG can still interfere with translation to a certain extent. However, it does not completely abolish translation and allows for the expression of certain proteins. The effectiveness of KSG depends on the nature of the mRNA residue preceding the start codon and is attenuated by translational coupling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Zachary D. Aron, Atousa Mehrani, Eric D. Hoffer, Kristie L. Connolly, Pooja Srinivas, Matthew C. Torhan, John N. Alumasa, Mynthia Cabrera, Divya Hosangadi, Jay S. Barbor, Steven C. Cardinale, Steven M. Kwasny, Lucas R. Morin, Michelle M. Butler, Timothy J. Opperman, Terry L. Bowlin, Ann Jerse, Scott M. Stagg, Christine M. Dunham, Kenneth C. Keiler
Summary: Bacterial ribosome rescue pathways are potential antibiotic targets that selectively inhibit the main ribosome rescue pathway trans-translation. Optimization of pharmacokinetic and antibiotic properties of acylaminooxadiazoles produced MBX-4132, effective in clearing multi-drug resistant Neisseria gonorrhoeae infection in mice. Structural analyses reveal a new mechanism for specific inhibition of trans-translation and a novel conformation within the bacterial ribosome critical for ribosome rescue pathways.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Yuxuan Zhou, Jingcheng Wu, Shihao Yao, Yulian Xu, Wenbin Zhao, Yunguang Tong, Zhan Zhou
Summary: In this study, we propose DeepCIP, a multimodal deep learning approach that uses both sequence and structural information to predict internal ribosome entry sites (IRESs) in circRNAs. Our results show that DeepCIP outperforms other methods in predicting circRNA IRESs. The analysis of the learned sequence patterns by DeepCIP aligns with previous discoveries of motifs facilitating circRNA translation. Therefore, DeepCIP has the potential to advance the study of circRNA coding potential and contribute to circRNA-based drug design.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Yutian Shao, Eliza Molestak, Weike Su, Marek Stankevic, Marek Tchorzewski
Summary: Fungal infections are a serious problem and new antifungal compounds are needed. Sordarin is a unique antifungal antibiotic that acts on the fungal translational machinery.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
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.
Article
Medicine, Research & Experimental
Paleerath Peerapen, Chanettee Chanthick, Visith Thongboonkerd
Summary: Caffeine and trigonelline, the major bioactive compounds in coffee, have hepatoprotective effects but their molecular mechanisms are unclear. Through proteomic and bioinformatic analyses, we identified altered proteins and revealed common and unique molecular mechanisms of caffeine and trigonelline in human hepatocytes. Ribosomal and translation regulatory proteins were found to play a key role, and induction of translational processes is a shared mechanism. This research provides insights for future clinical applications.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Hui Li, Yuhang Chen, Junshi Zhang, Yongquan Lin, Zhilong Yang, Juan Tan, Wentao Qiao
Summary: This study investigated the mechanism of upregulation of c-fos mRNA translation efficiency when cellular protein synthesis is shut off. The results showed that EV71 infection led to increased levels of c-Fos protein expression in rhabdomyosarcoma cells. Further analysis revealed the role of PCBP2 and La in regulating the IRES activity of c-fos, providing a novel target for gene translation regulation.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2021)
Article
Multidisciplinary Sciences
Yang Cao, Huachun Liu, Shannon S. Lu, Krysten A. Jones, Anitha P. Govind, Okunola Jeyifous, Christine Q. Simmons, Negar Tabatabaei, William N. Green, Jimmy. L. Holder Jr, Soroush Tahmasebi, Alfred L. George Jr, Bryan C. Dickinson
Summary: Translation-activating RNAs (taRNAs) are a bifunctional RNA-based molecular technology that can upregulate translation of target mRNAs. They can be delivered to various cells and tissues and have the potential for therapeutic RNA research.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Yanpeng Ma, Shixiang Zheng, Xiqiang Wang, Ling Zhu, Junkui Wang, Shuo Pan, Yong Zhang, Zhongwei Liu
Summary: This study investigates the translational regulatory mechanism of Delta-like ligand 4 (Dll4) high expression in macrophages exposed to advanced glycation end products (AGEs). The results show that AGEs exposure induces Dll4 5' untranslated region (5' UTR) IRES activity in human macrophages through the endoplasmic reticulum stress PERK/eIF2 alpha signaling pathway. hnRNPA1 is also found to be indispensable for AGEs-induced Dll4 5' UTR IRES activity in human macrophages.
Article
Biochemistry & Molecular Biology
Ka-Weng Ieong, Gabriele Indrisiunaite, Arjun Prabhakar, Joseph D. Puglisi, Mans Ehrenberg
Summary: The study revealed that m(6)A decreases the accuracy of reading sense and stop codons by reducing k(a) significantly more in cognate than near-cognate cases, leading to a significant increase in amino acid substitution errors in the process.
NUCLEIC ACIDS RESEARCH
(2021)