The DOI matches its Crossref record; 39 of the 40 references it cites were found in a registry or an index.
Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed
Open accessAbstract
Circular RNAs (circRNAs) are an endogenous class of animal RNAs. Despite their abundance, their function and expression in the nervous system are unknown. Therefore, we sequenced RNA from different brain regions, primary neurons, isolated synapses, as well as during neuronal differentiation. Using these and other available data, we discovered and analyzed thousands of neuronal human and mouse circRNAs. circRNAs were extraordinarily enriched in the mammalian brain, well conserved in sequence, often expressed as circRNAs in both human and mouse, and sometimes even detected in Drosophila brains. circRNAs were overall upregulated during neuronal differentiation, highly enriched in synapses, and often differentially expressed compared to their mRNA isoforms. circRNA expression correlated negatively with expression of the RNA-editing enzyme ADAR1. Knockdown of ADAR1 induced elevated circRNA expression. Together, we provide a circRNA brain expression atlas and evidence for important circRNA functions and values as biomarkers.
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In the citing paper
“Many circRNAs are significantly upregulated at different time points of neuron maturation in vitro.293”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [293]
In the citing paper
“They are highly expressed in the brain from the embryonic stage to adulthood and substantially upregulated during the differentiation and maturation of neurons.293”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [293]
In the citing paper
“CircRNAs maintain specificity and conservatism in the process of dynamic expression and are highly enriched in the mammalian brain, independent of linear transcripts [62].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [62]
In the citing paper
“CiRS-7 is abundantly expressed in the mammalian brain [49,62], where it increases the translation of the miR-7 target mRNA [14,49].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [62]
In the citing paper
“A study by Rybak et al. demonstrated that more than half of 15,849 mouse circRNAs, which are highly abundant, conserved, and dynamically expressed in the brain, are upregulated during the maturation of neurons [62,65].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [62]
In the citing paper
“Compared with other cytoplasmic RNAs, circRNAs seem to be more prone to being localized in synapses and their expression is correlated with neural plasticity, which further supports an important function of circRNAs in synaptic transmission [50,62].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [62]
Citations
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Circular RNAs are a large class of animal RNAs with regulatory potency
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Self-citationNatural RNA circles function as efficient microRNA sponges
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Combinatorial microRNA target predictions
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Self-citationCircular RNAs are abundant, conserved, and associated with ALU repeats
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circRNA biogenesis competes with pre-mRNA splicing
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Self-citationDetecting and characterizing circular RNAs
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The RNA Binding Protein Quaking Regulates Formation of circRNAs
Conn, S. J., Pillman, K. A., Toubia, J., Conn, V. M., Salmanidis, M., Phillips, C. A., Roslan, S., SCHREIBER, A. W., Gregory, P. A., & Goodall, G. J. (2015) · Cell · doi:10.1016/j.cell.2015.02.014 · Cited by 2,205
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Cited by
Sorted by citations
The biogenesis, biology and characterization of circular RNAs
Kristensen, L. S., Andersen, M. S., Stagsted, L. V. W., Ebbesen, K. K., Hansen, T. B., & Kjems, J. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0158-7 · Cited by 4,823
Endogenous microRNA sponges: evidence and controversy
Thomson, D. W., & Dinger, M. E. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.20 · Cited by 2,185
Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis
Legnini, I., Di Timoteo, G., Rossi, F., Morlando, M., Briganti, F., Sthandier, O., Fatica, A., Santini, T., Andronache, A., Wade, M., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.02.017 · Cited by 2,173
“Since circ-ZNF609 is highly expressed in neural tissues (Rybak-Wolf et al., 2015), we applied an established neuronal differentiation protocol (Wichterle and Peljto, 2008), and we checked for the expression of the FLAG-tagged circZNF609 RNA by northern blot in WT cells and in the F/D clone.”
BackgroundMethodInfluentialSelf-citationThe Biogenesis, Functions, and Challenges of Circular RNAs
Li, X., Yang, L. C., & Chen, L. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.06.034 · Cited by 2,060
Zheng, Q., Bao, C., Guo, W., Li, S., Chen, J., Chen, B., Luo, Y., Lyu, D., Li, Y., Shi, G., et al. (2016) · Nature Communications · doi:10.1038/ncomms11215 · Cited by 2,041
Metadata
- Authors
- Rybak-Wolf, A., Stottmeister, C., Glažar, P., Jens, M., Pino, N., Giusti, S., Hanan, M., Behm, M., Bartok, O., Ashwal-Fluss, R., Herzog, M., Schreyer, L., Papavasileiou, P., Ivanov, A., Öhman, M., Refojo, D., Kadener, S., & Rajewsky, N.
- Affiliations
- Max Delbrück Center (DE)
- Max Planck Institute of Psychiatry (DE)
- Hebrew University of Jerusalem (IL)
- Stockholm University (SE)
- Corresponding author
- Rajewsky, Nikolaus
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 58
- Issue
- 5
- Pages
- 870-885
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1991082489
- Semantic Scholar
- 2d5cc6120582eee013b4aab9138fa48d35f384f1
- Cited by
- 2,423
- References
- 40
- Citations by year
- 2026: 68 · 2025: 143 · 2024: 238 · 2023: 246 · 2022: 312 · 2021: 358 · 2020: 344 · 2019: 284 · 2018: 203 · 2017: 122 · 2016: 74 · 2015: 23
- FWCI
- 61.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Americanae (AECID Library) (publishedVersion, other-oa)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- 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 › Molecular Biology › RNA regulation and disease
- Keywords
- circular RNA, mammalian brain, neuronal differentiation, synapses, ADAR1, RNA editing, Drosophila brain, circRNA biomarkers
- MeSH terms
- RNA, Circular, Animals, Base Sequence, Brain, Cell Line, Drosophila melanogaster, Humans, Molecular Sequence Data, Organ Specificity, RNA, RNA, Messenger, Synapses, Sequence Analysis, DNA, Mice, Neurogenesis
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