RNA structure replaces the need for U2AF2 in splicing
- Chien-Ling Lin1,4,
- Allison J. Taggart1,4,
- Kian Huat Lim1,4,
- Kamil J. Cygan1,2,
- Luciana Ferraris1,
- Robbert Creton1,
- Yen-Tsung Huang3 and
- William G. Fairbrother1,2
- 1Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA;
- 2Center for Computational Molecular Biology, Brown University, Providence, Rhode Island 02912, USA;
- 3Departments of Epidemiology and Biostatistics, Brown University, Providence, Rhode Island 02912, USA
- Corresponding author: fairbrother{at}brown.edu
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↵4 These authors contributed equally to this work.
Abstract
RNA secondary structure plays an integral role in catalytic, ribosomal, small nuclear, micro, and transfer RNAs. Discovering a prevalent role for secondary structure in pre-mRNAs has proven more elusive. By utilizing a variety of computational and biochemical approaches, we present evidence for a class of nuclear introns that relies upon secondary structure for correct splicing. These introns are defined by simple repeat expansions of complementary AC and GT dimers that co-occur at opposite boundaries of an intron to form a bridging structure that enforces correct splice site pairing. Remarkably, this class of introns does not require U2AF2, a core component of the spliceosome, for its processing. Phylogenetic analysis suggests that this mechanism was present in the ancestral vertebrate lineage prior to the divergence of tetrapods from teleosts. While largely lost from land dwelling vertebrates, this class of introns is found in 10% of all zebrafish genes.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.181008.114.
- Received July 5, 2014.
- Accepted November 10, 2015.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six 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/.
