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

Cited 99
Views 3,782
Annotations

Cite this article as: eLife 2015;4:e07540 doi: 10.7554/eLife.07540

Article
Figures and data
Jump to

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.

Article and author information

Author details

Steven P Barrett

Department of Biochemistry, Stanford University School of Medicine, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Peter L Wang

Department of Biochemistry, Stanford University School of Medicine, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
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.

Reviewing Editor

Douglas L Black, Howard Hughes Medical Institute, University of California, Los Angeles, United States

Publication history

Received: March 19, 2015
Accepted: June 8, 2015
Accepted Manuscript published: June 9, 2015 (version 1)
Version of Record published: June 24, 2015 (version 2)

Copyright

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.