The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Combinatorial control of Drosophila circular RNA expression by intronic repeats, hnRNPs, and SR proteins
Open accessAbstract
Thousands of eukaryotic protein-coding genes are noncanonically spliced to produce circular RNAs. Bioinformatics has indicated that long introns generally flank exons that circularize in Drosophila, but the underlying mechanisms by which these circular RNAs are generated are largely unknown. Here, using extensive mutagenesis of expression plasmids and RNAi screening, we reveal that circularization of the Drosophila laccase2 gene is regulated by both intronic repeats and trans-acting splicing factors. Analogous to what has been observed in humans and mice, base-pairing between highly complementary transposable elements facilitates backsplicing. Long flanking repeats (∼400 nucleotides [nt]) promote circularization cotranscriptionally, whereas pre-mRNAs containing minimal repeats (<40 nt) generate circular RNAs predominately after 3′ end processing. Unlike the previously characterized Muscleblind (Mbl) circular RNA, which requires the Mbl protein for its biogenesis, we found that Laccase2 circular RNA levels are not controlled by Mbl or the Laccase2 gene product but rather by multiple hnRNP (heterogeneous nuclear ribonucleoprotein) and SR (serine–arginine) proteins acting in a combinatorial manner. hnRNP and SR proteins also regulate the expression of other Drosophila circular RNAs, including Plexin A (PlexA), suggesting a common strategy for regulating backsplicing. Furthermore, the laccase2 flanking introns support efficient circularization of diverse exons in Drosophila and human cells, providing a new tool for exploring the functional consequences of circular RNA expression across eukaryotes.
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Citations
Cites
Circular RNAs are a large class of animal RNAs with regulatory potency
Memczak, S., Jens, M., Elefsinioti, A., Torti, F., Krueger, J., Rybak, A., Maier, L., Mackowiak, S. D., Gregersen, L. H., Munschauer, M., et al. (2013) · Nature · doi:10.1038/nature11928 · Cited by 7,990
Natural RNA circles function as efficient microRNA sponges
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Circular RNAs are abundant, conserved, and associated with ALU repeats
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circRNA biogenesis competes with pre-mRNA splicing
Ashwal-Fluss, R., Meyer, M., Pamudurti, N. R., Ivanov, A., Bartok, O., Hanan, M., Evantal, N., Memczak, S., Rajewsky, N., & Kadener, S. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.019 · Cited by 3,083
Exon-intron circular RNAs regulate transcription in the nucleus
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Detecting and characterizing circular RNAs
Jeck, W. R., & Sharpless, N. E. (2014) · Nature Biotechnology · doi:10.1038/nbt.2890 · Cited by 2,702
Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed
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“…and recent deep sequencing studies have expanded this observation to thousands of circular RNAs expressed across eukaryotes, including humans (Salzman et al. 2012; Jeck et al. 2013; Memczak et al. 2013; Guo et al. 2014; Conn et al. 2015; Kelly et al. 2015), mice (Memczak et al. 2013;…”
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The RNA Binding Protein Quaking Regulates Formation of circRNAs
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Complementary Sequence-Mediated Exon Circularization
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“This is consistent with previous computational analyses (Jeck et al. 2013; Zhang et al. 2014) as well as experiments in humans (Liang and Wilusz 2014) and S. pombe (Barrett et al. 2015) that revealed a positive correlation between exon length and circularization efficiency.”
BackgroundResultInfluential
Cited by
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
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
The Biogenesis, Functions, and Challenges of Circular RNAs
Li, X., Yang, L., & Chen, L.-L. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.06.034 · Cited by 2,062
The biogenesis and emerging roles of circular RNAs
Chen, L.-L. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.32 · Cited by 1,743
The Landscape of Circular RNA in Cancer
Vo, J. N., Cieslik, M., Zhang, Y., Shukla, S., Xiao, L., Zhang, Y., Wu, Y.-M., Dhanasekaran, S. M., Engelke, C. G., Cao, X., et al. (2019) · Cell · doi:10.1016/j.cell.2018.12.021 · Cited by 1,738
Metadata
- Authors
- Kramer, M. C., Liang, D., Tatomer, D. C., Gold, B., March, Z. M., Cherry, S., & Wilusz, J. E.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2015-10-08
- Volume
- 29
- Issue
- 20
- Pages
- 2168-2182
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W1777808916
- Cited by
- 493
- References
- 48
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Kramer, M. C., Liang, D., Tatomer, D. C., Gold, B., March, Z. M., Cherry, S., & Wilusz, J. E. (2015). Combinatorial control of Drosophila circular RNA expression by intronic repeats, hnRNPs, and SR proteins. Genes & Development. https://doi.org/10.1101/gad.270421.115
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