Circular RNA biogenesis can proceed through an exon-containing lariat precursor

  1. Steven P Barrett
  2. Peter L Wang
  3. Julia Salzman  Is a corresponding author
  1. Stanford University School of Medicine, United States

Abstract

Pervasive expression of circular RNA is a recently discovered feature of eukaryotic gene expression programs, yet its function remains largely unknown. The presumed biogenesis of these RNAs involves a non-canonical 'backsplicing' event. Recent studies in mammalian cell culture posit that backsplicing is facilitated by inverted repeats flanking the circularized exon(s). Although such sequence elements are common in mammals, they are rare in lower eukaryotes, making current models insufficient to describe circularization. Through systematic splice site mutagenesis and the identification of splicing intermediates, we show that circular RNA in S. pombe is generated through an exon-containing lariat precursor. Furthermore, we have performed high-throughput and comprehensive mutagenesis of a circle-forming exon, which enabled us to discover a systematic effect of exon length on RNA circularization. Our results uncover a mechanism for circular RNA biogenesis that may account for circularization in genes that lack noticeable flanking intronic secondary structure.

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Author details

  1. Steven P Barrett

    Department of Biochemistry, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Peter L Wang

    Department of Biochemistry, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Julia Salzman

    Department of Biochemistry, Stanford University School of Medicine, Stanford, United States
    For correspondence
    julia.salzman@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2015, Barrett et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Steven P Barrett
  2. Peter L Wang
  3. Julia Salzman
(2015)
Circular RNA biogenesis can proceed through an exon-containing lariat precursor
eLife 4:e07540.
https://doi.org/10.7554/eLife.07540

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https://doi.org/10.7554/eLife.07540