Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor
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Circular RNAs (circRNAs) are widespread circles of non-coding RNAs with largely unknown function. Because stimulation of mammary cells with the epidermal growth factor (EGF) leads to dynamic changes in the abundance of coding and non-coding RNA molecules, and culminates in the acquisition of a robust migratory phenotype, this cellular model might disclose functions of circRNAs. Here we show that circRNAs of EGF-stimulated mammary cells are stably expressed, while mRNAs and microRNAs change within minutes. In general, the circRNAs we detected are relatively long-lived and weakly expressed. Interestingly, they are almost ubiquitously co-expressed with the corresponding linear transcripts, and the respective, shared promoter regions are more active compared to genes producing linear isoforms with no detectable circRNAs. These findings imply that altered abundance of circRNAs, unlike changes in the levels of other RNAs, might not play critical roles in signaling cascades and downstream transcriptional networks that rapidly commit cells to specific outcomes.
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Endogenous circRNAs lack the free ends necessary for exonuclease-mediated degradation, rendering them resistant to several mechanisms of RNA turnover and granting them extended lifespans compared to linear mRNA counterparts.
“endogenous circRNAs lack the free ends necessary for exonuclease-mediated degradation, rendering them resistant to several mechanisms of RNA turnover and granting them extended lifespans as compared to their linear mRNA counterparts2, 9.”
From Engineering circular RNA for potent and stable translation in eukaryotic cells (2018) · cites this paper as [9]
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- Authors
- Enuka, Y., Lauriola, M., Feldman, M. E., Sas-Chen, A., Ulitsky, I., & Yarden, Y.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Yarden, Yosef
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-12-10
- Volume
- 44
- Issue
- 3
- Pages
- 1370-1383
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC4756822
- OpenAlex
- W2285247593
- Cited by
- 757
- References
- 64
- Citations by year
- 2026: 66 · 2025: 91 · 2024: 100 · 2023: 105 · 2022: 93 · 2021: 107 · 2020: 68 · 2019: 57 · 2018: 33 · 2017: 26 · 2016: 9 · 2013: 1
- FWCI
- 9.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by-nc)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- circular RNA, epidermal growth factor, mammary epithelial cells, RNA stability, non-coding RNA, microRNA, cell migration, growth factor signaling
- MeSH terms
- RNA, Circular, Breast, Cell Line, Epidermal Growth Factor, Epithelial Cells, Humans, RNA, RNA, Messenger, Gene Expression, Transforming Growth Factor alpha, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, RNA Stability, MicroRNAs, Heparin-binding EGF-like Growth Factor
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