Long-range RNA pairings contribute to mutually exclusive splicing
- Yuan Yue1,3,
- Yun Yang1,3,
- Lanzhi Dai1,
- Guozheng Cao1,
- Ran Chen1,
- Weiling Hong1,
- Baoping Liu1,
- Yang Shi1,
- Yijun Meng1,
- Feng Shi1,
- Mu Xiao2 and
- Yongfeng Jin1
- 1Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, ZJ310058, China
- 2Institute of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, ZJ310058, China
- Corresponding author: jinyf{at}zju.edu.cn
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↵3 These authors contributed equally to this work.
Abstract
Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of the Dscam exon cluster. Here, we reveal a molecular model for the regulation of the mutually exclusive splicing of the serpent pre-mRNA based on competition between upstream and downstream RNA pairings. Such dual RNA pairings confer fine tuning of the inclusion of alternative exons. Moreover, we demonstrate that the splicing outcome of alternative exons is mediated in relative pairing strength-correlated mode. Combined comparative genomics analysis and experimental evidence revealed similar bidirectional structural architectures in exon clusters 4 and 9 of the Dscam gene. Our findings provide a novel mechanistic framework for the regulation of mutually exclusive splicing and may offer potentially applicable insights into long-range RNA–RNA interactions in gene regulatory networks.
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Footnotes
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.053314.115.
- Received July 15, 2015.
- Accepted October 6, 2015.
This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
