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IRES-mediated cap-independent translation, a path leading to hidden proteome
Open accessAbstract
Most eukaryotic mRNAs are translated in a cap-dependent fashion; however, under stress conditions, the cap-independent translation driven by internal ribosomal entry sites (IRESs) can serve as an alternative mechanism for protein production. Many IRESs have been discovered from viral or cellular mRNAs to promote ribosome assembly and initiate translation by recruiting different trans-acting factors. Although the mechanisms of translation initiation driven by viral IRESs are relatively well understood, the existence of cellular IRESs is still under debate due to the limitations of translation reporter systems used to assay IRES activities. A recent screen identified > 1000 putative IRESs from viral and human mRNAs, expanding the scope and mechanism for cap-independent translation. Additionally, a large number of circular RNAs lacking free ends were identified in eukaryotic cells, many of which are found to be translated through IRESs. These findings suggest that IRESs may play a previously unappreciated role in driving translation of the new type of mRNA, implying a hidden proteome produced from cap-independent translation.
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Biagi, M. C., Giuliani, A., Grandioso, A., Timoteo, G. D., & Bozzoni, I. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.13.653105 · Cited by 1
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Xiao, W., Hann, T., Perry, Z. R., Pandey, V., Cheng, J., Wohlschlegel, J., Pyle, A. M., & Black, D. L. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.11.705401 · Cited by 1
Evaluating the reliability of tools for mRNA annotation and IRES studiesPreprint
May, G., Akirtava, C., & McManus, C. J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.29.707813 · Cited by 4
Sychla, A., Bongrand, P., Yang, G., Krishnan, A., Rulison, J., Wesselhoeft, R. A., Bisaria, N., & Rouskin, S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.19.726202 · Cited by 2
A joint adventure of Sino-German researchers to explore the wild world of RNAs
Bindereif, A., & Wang, Z. (2019) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjz097
Regulatory RNAs in cardiovascular disease
Madè, A., Greco, S., & Martelli, F. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822258-4.00019-5
The Emerging Role of Pyruvate Kinase M2 in Regulating Glutaminolysis via c-Myc
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Metadata
- Authors
- Yang, Y., & Wang, Z.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Yang, Yun
- Wang, Zefeng
- Venue
- Journal of Molecular Cell Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-09-03
- Volume
- 11
- Issue
- 10
- Pages
- 911-919
- ISSN
- 1674-2788 (ISSN-L)
- 1759-4685
- PMC
- PMC6884710
- OpenAlex
- W2971386099
- Cited by
- 260
- References
- 80
- Citations by year
- 2026: 30 · 2025: 45 · 2024: 53 · 2023: 39 · 2022: 43 · 2021: 32 · 2020: 17 · 2019: 1
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Molecular Cell Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Youth Innovation Promotion Association CAS and Shanghai Science and Technology Committee Rising-Star Program (19QA1410500)
- CAS Pioneer 100-Talent Program
- National Natural Science Foundation of China (31870814, 91753135, 31730110, 31661143031, 31570823)
- 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 › PI3K/AKT/mTOR signaling in cancer
- Keywords
- internal ribosome entry site, cap-independent translation, circular RNA, translation initiation, trans-acting factors
- MeSH terms
- Internal Ribosome Entry Sites, Humans, Models, Biological, Ribosomes, Protein Biosynthesis, Proteome
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