ArticleJournal of cellular biochemistry2010
The human IGF1R IRES likely operates through a Shine-Dalgarno-like interaction with the G961 loop (E-site) of the 18S rRNA and is kinetically modulated by a naturally polymorphic polyU loop.
Article in Journal of cellular biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- 5'-UTR G-Quadruplex-Mediated Translation Regulation in Eukaryotes: Current Understanding and Methodological Challenges.International journal of molecular sciences · 2025Review
- Decryption of sequence, structure, and functional features of SINE repeat elements in SINEUP non-coding RNA-mediated post-transcriptional gene regulation.Nature communications · 2024Article
- Promising Assays for Examining a Putative Role of Ribosomal Heterogeneity in COVID-19 Susceptibility and Severity.Life (Basel, Switzerland) · 2022Review
- Alteration of ribosome function upon 5-fluorouracil treatment favors cancer cell drug-tolerance.Nature communications · 2022Article
- Structured elements drive extensive circular RNA translation.Molecular cell · 2021Article
- REDD1 is a determinant of low-dose metronomic doxorubicin-elicited endothelial cell dysfunction through downregulation of VEGFR-2/3 expression.Experimental & molecular medicine · 2021Article
- Negative charge in the RACK1 loop broadens the translational capacity of the human ribosome.Cell reports · 2021Article
- A PRC2-independent function for EZH2 in regulating rRNA 2'-O methylation and IRES-dependent translation.Nature cell biology · 2021Article
- Exploring the Role of AUG Triplets in Human Cap-Independent Translation Enhancing Elements.Biochemistry · 2018Article
- Translation acrobatics: how cancer cells exploit alternate modes of translational initiation.EMBO reports · 2018Review
- Interaction of rRNA with mRNA and tRNA in Translating Mammalian Ribosome: Functional Implications in Health and Disease.Biomolecules · 2018Review
- Insights into Structural and Mechanistic Features of Viral IRES Elements.Frontiers in microbiology · 2017Review
- Translational Dysregulation in Cancer: Molecular Insights and Potential Clinical Applications in Biomarker Development.Frontiers in oncology · 2017Review
- IRES inhibition induces terminal differentiation and synchronized death in triple-negative breast cancer and glioblastoma cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Small molecule inhibitors of IRES-mediated translation.Cancer biology & therapy · 2015Article
- The mRNA of human cytoplasmic arginyl-tRNA synthetase recruits prokaryotic ribosomes independently.The Journal of biological chemistry · 2014Article
- p53 acts as a safeguard of translational control by regulating fibrillarin and rRNA methylation in cancer.Cancer cell · 2013Article
- Measuring microsatellite conservation in mammalian evolution with a phylogenetic birth-death model.Genome biology and evolution · 2012Article
- Cellular IRES-mediated translation: the war of ITAFs in pathophysiological states.Cell cycle (Georgetown, Tex.) · 2011Review
- Mining Functional Elements in Messenger RNAs: Overview, Challenges, and Perspectives.Frontiers in plant science · 2011Article
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
IGF1R is a proto-oncogene with potent mitogenic and antiapoptotic activities, and its expression must be tightly regulated to maintain normal cellular and tissue homeostasis. We previously demonstrated that translation of the human IGF1R mRNA is controlled by an internal ribosome entry site (IRES), and delimited the core functional IRES to a 90-nucleotide segment of the 5'-untranslated region positioned immediately upstream of the initiation codon. Here we have analyzed the sequence elements that contribute to the function of the core IRES. The Stem2/Loop2 sequence of the IRES exhibits near-perfect Watson-Crick complementarity to the G961 loop (helix 23b) of the 18S rRNA, which is positioned within the E-site on the platform of the 40S ribosomal subunit. Mutations that disrupt this complementarity have a negative impact on regulatory protein binding and dramatically decrease IRES activity, suggesting that the IGF1R IRES may recruit the 40S ribosome by a eukaryotic equivalent of the Shine-Dalgarno (mRNA-rRNA base-pairing) interaction. The homopolymeric Loop3 sequence of the IRES modulates accessibility and limits the rate of translation initiation mediated through the IRES. Two functionally distinct allelic forms of the Loop3 poly(U)-tract are prevalent in the human population, and it is conceivable that germ-line or somatic variations in this sequence could predispose individuals to development of malignancy, or provide a selectable growth advantage for tumor cells.
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