Cited by 1,999Circular RNAs in diseasesRNA Research and SplicingRNA regulation and disease

Complementary Sequence-Mediated Exon Circularization

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Zhang, Xiao-Ou, Wang, Hai-Bin, Zhang, Yang, Lu, Xuhua, Chen, Ling-Ling, Yang, Li·2014·Cell

Abstract

Exon circularization has been identified from many loci in mammals, but the detailed mechanism of its biogenesis has remained elusive. By using genome-wide approaches and circular RNA recapitulation, we demonstrate that exon circularization is dependent on flanking intronic complementary sequences. Such sequences and their distribution exhibit rapid evolutionary changes, showing that exon circularization is evolutionarily dynamic. Strikingly, exon circularization efficiency can be regulated by competition between RNA pairing across flanking introns or within individual introns. Importantly, alternative formation of inverted repeated Alu pairs and the competition between them can lead to alternative circularization, resulting in multiple circular RNA transcripts produced from a single gene. Collectively, exon circularization mediated by complementary sequences in human introns and the potential to generate alternative circularization products extend the complexity of mammalian posttranscriptional regulation.

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Crossref · 10.1016/j.cell.2014.09.001

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  • CircRNA is a highly stable single-stranded RNA with a covalently closed loop structure.

    “CircRNA is a highly stable single-stranded RNA with a covalently closed loop structure (Fig. 3), including a large category of non-coding RNAs generated by backsplicing in eukaryotic cells.218–220”

    From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [218]

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Authors
Zhang, X.-O., Wang, H.-B., Zhang, Y., Lu, X., Chen, L.-L., & Yang, L.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Second Military Medical University (CN)
Corresponding author
  • Chen, Ling-Ling
  • Yang, Li
Venue
Cell
Publisher
Elsevier BV
Published
2014-09
Volume
159
Issue
1
Pages
134-147
ISSN
0092-8674 (ISSN-L)
OpenAlex
W1981726010
Cited by
1,999
References
35
Citations by year
2026: 70 · 2025: 117 · 2024: 200 · 2023: 183 · 2022: 254 · 2021: 280 · 2020: 245 · 2019: 212 · 2018: 176 · 2017: 121 · 2016: 74 · 2015: 54 · 2014: 9
FWCI
35.28
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (31271376, 2014CB964800, 31322018)
  • Max-Planck-Gesellschaft
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, Alu elements, inverted repeats, post-transcriptional regulation, intron evolution, mammalian gene expression
MeSH terms
Animals, Base Sequence, Exons, Humans, Introns, Mammals, Molecular Sequence Data, Nucleic Acid Conformation, Genome, Human, Sequence Alignment, Alternative Splicing, Evolution, Molecular, Alu Elements, Embryonic Stem Cells

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