Translation of CircRNAs
Open accessAbstract
Circular RNAs (circRNAs) are abundant and evolutionarily conserved RNAs of largely unknown function. Here, we show that a subset of circRNAs is translated in vivo. By performing ribosome footprinting from fly heads, we demonstrate that a group of circRNAs is associated with translating ribosomes. Many of these ribo-circRNAs use the start codon of the hosting mRNA, are bound by membrane-associated ribosomes, and have evolutionarily conserved termination codons. In addition, we found that a circRNA generated from the muscleblind locus encodes a protein, which we detected in fly head extracts by mass spectrometry. Next, by performing in vivo and in vitro translation assays, we show that UTRs of ribo-circRNAs (cUTRs) allow cap-independent translation. Moreover, we found that starvation and FOXO likely regulate the translation of a circMbl isoform. Altogether, our study provides strong evidence for translation of circRNAs, revealing the existence of an unexplored layer of gene activity.
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A small number of circRNAs can be translated despite lacking both terminal 5′ and 3′ ends.
“Emerging evidence indicates that a small number of circRNAs can be translated despite lacking both terminal 5 ′ and 3 ′ ends [53,55,56].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [56]
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- Authors
- Pamudurti, N. R., Bartok, O., Jens, M., Ashwal-Fluss, R., Stottmeister, C., Ruhe, L., Hanan, M., Wyler, E., Perez-Hernandez, D., Ramberger, E., Shenzis, S., Samson, M., Dittmar, G., Landthaler, M., Chekulaeva, M., Rajewsky, N., & Kadener, S.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Max Delbrück Center (DE)
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 66
- Issue
- 1
- Pages
- 9-21.e7
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC5387669
- OpenAlex
- W2600581473
- Cited by
- 1,810
- References
- 55
- Citations by year
- 2026: 90 · 2025: 140 · 2024: 189 · 2023: 175 · 2022: 242 · 2021: 295 · 2020: 279 · 2019: 193 · 2018: 147 · 2017: 57
- FWCI
- 75.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- ERC Consolidator Grant (647989)
- Einstein Foundation
- Berlin School of Integrative Oncology (GSC 1091)
- DFG (GRK 1772)
- BIF
- JBC fellowship
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- 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
- Keywords
- circular RNA, circRNA translation, ribosome profiling, cap-independent translation, stop codon, starvation, FOXO, Drosophila
- MeSH terms
- RNA, Circular, Animals, Cell Line, Drosophila melanogaster, Genotype, Head, Mutation, Nuclear Proteins, Nucleic Acid Conformation, Nutritional Status, Phenotype, Ribosomes, RNA, RNA Caps, Mass Spectrometry, Starvation, Structure-Activity Relationship, Transfection, Protein Biosynthesis, Codon, Initiator, Codon, Terminator, Drosophila Proteins, Mice, Rats, Forkhead Transcription Factors
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