ArticleProceedings of the National Academy of Sciences of the United States of America2000
A 9-nt segment of a cellular mRNA can function as an internal ribosome entry site (IRES) and when present in linked multiple copies greatly enhances IRES activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 242 citations in OpenAlex.
- Current Practice in Bicistronic IRES Reporter Use: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Unbiased screen of human transcriptome reveals an unexpected role of 3'UTRs in translation initiation.Nature communications · 2026Article
- The Cap-Independent Translation of Survivin 5'UTR and HIV-1 IRES Sequences Is Inhibited by Oxidative Stress Produced byBiomolecules · 2026Article
- Development and Characterization of an Oncolytic Human Adenovirus-Based Vector Co-Expressing the Adenovirus Death Protein and p14 Fusion-Associated Small Transmembrane Fusogenic Protein.International journal of molecular sciences · 2024Article
- A circular split nanoluciferase reporter for validating and screening putative internal ribosomal entry site elements.RNA (New York, N.Y.) · 2024Article
- Modeling alternative translation initiation sites in plants reveals evolutionarily conservedGenome research · 2024Article
- Cap-Independent Circular mRNA Translation Efficiency.Vaccines · 2023Review
- Article
- Internal ribosomal entry site-mediated translational activity of nitric oxide synthase 2.Animal cells and systems · 2023Article
- SFPQ promotes RAS-mutant cancer cell growth by modulating 5'-UTR mediated translational control of CK1α.NAR cancer · 2022Article
- Pervasive translation of circular RNAs driven by short IRES-like elements.Nature communications · 2022Article
- Protein synthesis control in cancer: selectivity and therapeutic targeting.The EMBO journal · 2022Review
- Review
- Synthetic polycistronic sequences in eukaryotes.Synthetic and systems biotechnology · 2021Review
- Characterization ofFrontiers in plant science · 2021Article
- A Novel Cis-Acting RNA Structural Element Embedded in the Core Coding Region of the Hepatitis C Virus Genome Directs Internal Translation Initiation of the Overlapping Core+1 ORF.International journal of molecular sciences · 2020Article
- Dengue and Zika Virus 5' Untranslated Regions Harbor Internal Ribosomal Entry Site Functions.mBio · 2019Article
- Noncanonical Translation Initiation in Eukaryotes.Cold Spring Harbor perspectives in biology · 2019Review
- The 5' Untranslated Region of the Capsid Protein 2 Gene of Mink Enteritis Virus Is Essential for Its Expression.Journal of virology · 2018Article
- A highly sensitive trap vector system for isolating reporter cells and identification of responsive genes.Biology methods & protocols · 2018Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study addresses the properties of a newly identified internal ribosome entry site (IRES) contained within the mRNA of the homeodomain protein Gtx. Sequential deletions of the 5' untranslated region (UTR) from either end did not define distinct IRES boundaries; when five nonoverlapping UTR fragments were tested, four had IRES activity. These observations are consistent with other cellular IRES analyses suggesting that some cellular IRESes are composed of segments (IRES modules) that independently and combinatorially contribute to overall IRES activity. We characterize a 9-nt IRES module from the Gtx 5' UTR that is 100% complementary to the 18S rRNA at nucleotides 1132-1124. In previous work, we demonstrated that this mRNA segment could be crosslinked to its complement within intact 40S subunits. Here we show that increasing the number of copies of this IRES module in the intercistronic region of a dicistronic mRNA strongly enhances IRES activity in various cell lines. Ten linked copies increased IRES activity up to 570-fold in Neuro 2a cells. This level of IRES activity is up to 63-fold greater than that obtained by using the well characterized encephalomyocarditis virus IRES when tested in the same assay system. When the number of nucleotides between two of the 9-nt Gtx IRES modules was increased, the synergy between them decreased. In light of these findings, we discuss possible mechanisms of ribosome recruitment by cellular mRNAs, address the proposed role of higher order RNA structures on cellular IRES activity, and suggest parallels between IRES modules and transcriptional enhancer elements.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.