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)
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
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
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)
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
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
Medicine, Research & Experimental
Te Bu, Zhelong Li, Ying Hou, Wenqi Sun, Rongxin Zhang, Lianbi Zhao, Mengying Wei, Guodong Yang, Lijun Yuan
Summary: A nano-system has been developed to deliver inflammation-responsive Il-10 mRNA preferentially into macrophages for tailored inflammation control, showing promising potential for treating inflammatory diseases like atherosclerosis.
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
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
Biotechnology & Applied Microbiology
Xinjie Chen, Chen Wang, Yuan Lu
Summary: Facing the development of mRNA technology in medicine and vaccines, circular mRNA (circmRNA) has gained traction as a promising alternative due to its circular secondary structure and higher stability. This study explores different strategies for circmRNA biosynthesis through ribozyme catalysis and enzymatic reactions. The chosen methods, T4 Rnl 2 and Td ribozyme, show significant differences in ligation efficiency, with T4 Rnl 2 resulting in an 86% higher expression level of circmRNA. The screening of IRES sequences reveals mud crab dicistrovirus IRES as a high-efficiency sequence for translation in mammalian cells. These findings hold promise for the industrial production of circmRNAs and the development of mRNA vaccines, expanding the potential applications of circmRNAs in biomedicine.
BIOTECHNOLOGY AND BIOENGINEERING
(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
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
Biotechnology & Applied Microbiology
Ricardo Vieira, John N. Mariani, Nguyen P. T. Huynh, Hans J. T. Stephensen, Renee Solly, Ashley Tate, Steven Schanz, Natasha Cotrupi, Marzieh Mousaei, Jon Sporring, Abdellatif Benraiss, Steven A. Goldman
Summary: Aged or diseased human glial cells can be replaced by younger and healthy glial progenitor cells in the adult brain. This study suggests a potential therapeutic strategy for replacing aged and diseased human glia.
NATURE BIOTECHNOLOGY
(2023)
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)
Article
Multidisciplinary Sciences
Mikael Holm, S. Kundhavai Natchiar, Emily J. Rundlet, Alexander G. Myasnikov, Zoe L. Watson, Roger B. Altman, Hao-Yuan Wang, Jack Taunton, Scott C. Blanchard
Summary: In all species, ribosomes synthesize proteins by decoding mRNA nucleotide sequences. While knowledge of the decoding mechanism is derived from bacterial systems, eukaryotes achieve higher fidelity decoding. Changes in decoding fidelity in humans are linked to aging and disease and have therapeutic implications. This study reveals that the molecular basis of ribosome fidelity in humans is kinetically and structurally distinct from bacteria, due to eukaryote-specific structural elements in the ribosome and elongation factor eEF1A.
Article
Biochemistry & Molecular Biology
Lu-Yi Jiang, Wei Jiang, Na Tian, Yan-Ni Xiong, Jie Liu, Jian Wei, Kai-Yue Wu, Jie Luo, Xiong-Jie Shi, Bao-Liang Song
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Ao Hu, Xue-Tong Zhao, Heng Tu, Ting Xiao, Ting Fu, Yan Wang, Yong Liu, Xiong-Jie Shi, Jie Luo, Bao-Liang Song
JOURNAL OF LIPID RESEARCH
(2018)
Review
Biochemistry & Molecular Biology
Jie Luo, Lu-Yi Jiang, Hongyuan Yang, Bao-Liang Song
TRENDS IN BIOCHEMICAL SCIENCES
(2019)
Article
Genetics & Heredity
Shi-You Jiang, Jing-Jie Tang, Xu Xiao, Wei Qi, Suqian Wu, Chao Jiang, Jiaxu Hong, Jianjiang Xu, Bao-Liang Song, Jie Luo
Article
Biochemistry & Molecular Biology
Elaina M. Melton, Haibo Li, Jalen Benson, Paul Sohn, Li-Hao Huang, Bao-Liang Song, Bo-Liang Li, Catherine C. Y. Chang, Ta-Yuan Chang
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Review
Cell Biology
Jie Luo, Hongyuan Yang, Bao-Liang Song
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2020)
Letter
Cell Biology
Fangfang Han, Xiao Liu, Chuanfang Chen, Yinan Liu, Mingkun Du, Yu Zhou, Yong Liu, Bao-Liang Song, Housheng Hansen He, Yan Wang
Article
Genetics & Heredity
Bo-Tao Li, Ming Sun, Yun-Feng Li, Ju-Qiong Wang, Zi-Mu Zhou, Bao-Liang Song, Jie Luo
Article
Cell Biology
Jian Xiao, Yanni Xiong, Liu-Ting Yang, Ju-Qiong Wang, Zi-Mu Zhou, Le-Wei Dong, Xiong-Jie Shi, Xiaolu Zhao, Jie Luo, Bao-Liang Song
Summary: The study identifies POST1 as a crucial gene involved in the SREBP signaling pathway, promoting the generation of functional S1P-C'/C and regulating protein cleavage. POST1 plays important roles in maintaining lipid homeostasis, unfolded protein response, lipoprotein metabolism, and lysosome biogenesis.
Article
Cell Biology
Liping Chu, Yuxiu Qu, Yang An, Linjun Hou, Juewan Li, Weijia Li, Gaofeng Fan, Bao-Liang Song, En Li, Liye Zhang, Wei Qi
Summary: This study investigates the pharmacological mechanism of the PRC2 inhibitor MAK683 and identifies a group of senescence-associated genes that are derepressed upon PRC2 inhibition, leading to tumor regression and improved therapeutic efficacy. Furthermore, the combination of PRC2 inhibitors and CDK4/6 inhibitors shows even better effects, providing a novel strategy for clinical treatment.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Zhi-Ping Qiu, Zi-Cun Lin, Ao Hu, Yuan-Bin Liu, Wan-Er Zeng, Xiaolu Zhao, Xiong-Jie Shi, Jie Luo, Bao-Liang Song
Summary: The Hedgehog (Hh) signaling pathway is important for embryonic development. The interaction between Hh and PTCH1 regulates the activity of SMO, a key protein in the pathway. Cholesterol modification of SMO in the endoplasmic reticulum (ER) is regulated by Hh and PTCH1, and it affects the localization and function of SMO. The transport of cholesterol by GRAMD1/ASTER proteins plays a role in SMO maturation and Hh signaling.
Article
Cell Biology
Yu-Xia Zhou, Jian Wei, Gang Deng, Ao Hu, Pu-Yu Sun, Xiaolu Zhao, Bao-Liang Song, Jie Luo
Summary: This study identifies an intracellular transport pathway of LDL-LDL receptor that bypasses lysosomes and delivers cholesterol to mitochondria for steroidogenesis.
NATURE CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nan Zhao, Gang Deng, Pei-Xin Yuan, Ya-Fen Zhang, Lu-Yi Jiang, Xiaolu Zhao, Bao-Liang Song
Summary: The previously unannotated protein TMEM241 is found to play a crucial role in cholesterol egress from lysosomes. It transports UDP-N-acetylglucosamine (UDP-GlcNAc) into the Golgi lumen, which is used for the modification of proteins like NPC2. Loss of TMEM241 leads to cholesterol accumulation in lysosomes due to impaired lysosomal targeting of NPC2.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Ju-Qiong Wang, Zi-Cun Lin, Liang-Liang Li, Shao-Fang Zhang, Wei-Hui Li, Wei Liu, Bao-Liang Song, Jie Luo
Summary: This study shows that IDOL can be modified by SUMOylation, which counteracts its ubiquitination and increases IDOL protein levels. Additionally, SENP1 modulates the LDLR pathway by deSUMOylating IDOL, thus influencing LDLR protein levels and LDL endocytosis. These findings suggest potential therapeutic implications for cardiovascular disease.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Endocrinology & Metabolism
Binlu Huang, Bao-Liang Song, Chenqi Xu