IRES elements are highly structured RNA sequences that function to recruit ribosomes for the initiation of translation. In contrast to the canonical cap-binding, ribosome-scanning model, the mechanism of IRES-mediated translation initiation is not well understood. IRES elements, first discovered in viral RNA genomes, were subsequently found in a subset of cellular RNAs as well. Interestingly, these cellular IRES-containing mRNAs appear to play important roles during conditions of cellular stress, development, and disease (e.g., cancer). It has been shown for viral IRESes that some require specific IRES trans-acting factors (ITAFs), while others require few if any additional proteins and can bind ribosomes directly. Current studies are aimed at elucidating the mechanism of IRES-mediated translation initiation and features that may be common or differ greatly among cellular and viral IRESes. This review will explore IRES elements as important RNA structures that function in both cellular and viral RNA translation and the significance of these structures in providing an alternative mechanism of eukaryotic translation initiation.
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http://dx.doi.org/10.1016/j.bbagrm.2009.07.004 | DOI Listing |
Medicina (Kaunas)
January 2025
Department of Neurosurgery, University of Medicine and Pharmacy "Carol Davila", 030147 Bucharest, Romania.
: The Index of Response to Stimulation (IRES) is a new index that we introduce in this study to grade the effectiveness of vagus nerve stimulation in the treatment of drug-resistant epilepsy. We assessed 76 patients at 6, 12, and 18 months after VNS evaluating improvement with the IRES in four key dimensions: seizure duration decrease, seizure intensity decrease, improvement in quality of life, and seizure frequency decrease. This scale goes from 0, meaning no improvement, to 8, meaning maximal improvement, making the scale a really good measure of clinical utility.
View Article and Find Full Text PDFTheranostics
January 2025
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Circular RNA (circRNA) has gained attention as a promising platform for mRNA vaccines due to its stability, sustained protein expression, and intrinsic immunostimulatory properties. This study aimed to design and optimize a circRNA cancer vaccine platform by screening for efficient internal ribosome entry sites (IRES) and enhancing circRNA translation efficiency for improved cancer immunotherapy. We screened 29 IRES elements to identify the most efficient one for immune cell translation, ultimately discovering the A (EV-A) IRES.
View Article and Find Full Text PDFPharmaceuticals (Basel)
December 2024
Department of Life Science, College of Science and General Studies, Alfaisal University, Riyadh 11533, Saudi Arabia.
The hallmark of Alzheimer's disease (AD) is the buildup of amyloid-β (Aβ), which is produced when the amyloid precursor protein (APP) misfolds and deposits as neurotoxic plaques in the brain. A functional iron responsive element (IRE) RNA stem loop is encoded by the APP 5'-UTR and may be a target for regulating the production of Alzheimer's amyloid precursor protein. Since modifying Aβ protein expression can give anti-amyloid efficacy and protective brain iron balance, targeted regulation of amyloid protein synthesis through modulation of 5'-UTR sequence function is a novel method for the prospective therapy of Alzheimer's disease.
View Article and Find Full Text PDFThe pseudouridine synthase DKC1 regulates internal ribosome entry site (IRES)-dependent translation and is upregulated in cancers by the MYC family of oncogenic transcription factors. We investigated the functional significance of DKC1 in MYCN-amplified neuroblastoma and its underlying mechanisms. A key function of DKC1 is to promote an ATF4-mediated gene expression program for amino acid metabolism and stress adaptation.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Department of Pathophysiology, School of Basic Medical Sciences, The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, State Key Laboratory of Esophageal, Cancer Prevention and Treatment, Provincial Cooperative Innovation Center for Cancer Chemoprevention, China-US (Henan) Hormel Cancer Institute, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, 450000, China.
Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of esophageal cancer cases. The lack of effective therapeutic targets makes it difficult to improve the overall survival of patients with ESCC. Reticulon 4 Interacting Protein 1 (RTN4IP1) is a novel mitochondrial oxidoreductase.
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