Systematic discovery of cap-independent translation sequences in human and viral genomes
Abstract
Identifying the IRESs of humans and viruses: Most proteins result from the translation of 5′ capped RNA transcripts. In viruses and a subset of human genes, RNA transcripts with internal ribosome entry sites (IRESs) are uncapped. Weingarten-Gabbay et al. systematically surveyed the presence of IRESs in human protein-coding transcripts, as well those of viruses (see the Perspective by Gebauer and Hentze). Large-scale mutagenesis profiling identified two classes of IRESs: those having a functional element localized to one small region of the IRES and those with important elements distributed across the entire region. An unbiased screen across human genes suggests that IRESs are more frequent than previously supposed in 3′ untranslated regions. Science , this issue p. 10.1126/science.aad4939 ; see also p. 228
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The finding that cap-independent 5′ UTRs have poor translation rate is consistent with previous studies showing IRES are more efficient under stress conditions.
“Our results demonstrated that cap-independent 5′ UTRs exhibited a poor translation rate across three different cell lines compared to cap-dependent 5′ UTRs, which is consistent with previous studies showing that IRES are more efficient under stress conditions.42,43”
From Evaluation of synthetic mRNA with selected UTR sequences and alternative poly(A) tail, in vitro and in vivo (2025) · cites this paper as [42]
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- Authors
- Weingarten-Gabbay, S., Elias-Kirma, S., Nir, R., Gritsenko, A. A., Stern-Ginossar, N., Yakhini, Z., Weinberger, A., & Segal, E.
- Affiliations
- Weizmann Institute of Science (IL)
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
- Delft University of Technology (NL)
- Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
- Department of Computer Science, Technion, Haifa, Israel.
- Corresponding author
- Segal, Eran
- Venue
- Science
- Published
- 2016-01-15
- Volume
- 351
- Issue
- 6270
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2234324103
- Cited by
- 334
- References
- 0
- Citations by year
- 2026: 31 · 2025: 23 · 2024: 25 · 2023: 32 · 2022: 25 · 2021: 37 · 2020: 39 · 2019: 27 · 2018: 40 · 2017: 31 · 2016: 23
- FWCI
- 17.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH
- European Research Council (ERC)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- cap-independent translation, 3' untranslated region, translational regulation, 18S rRNA, secondary structure, human genome, viral genome
- MeSH terms
- Internal Ribosome Entry Sites, Humans, Oligonucleotides, RNA Caps, RNA Viruses, RNA, Ribosomal, 18S, Protein Biosynthesis, Genome, Human, Gene Expression Regulation, Viral, Mutagenesis, Genome, Viral, Sequence Analysis, DNA, Sequence Analysis, RNA, Base Pairing, 5' Untranslated Regions, 3' Untranslated Regions, High-Throughput Nucleotide Sequencing
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