RNA editing in nascent RNA affects pre-mRNA splicing
- Yun-Hua Esther Hsiao1,
- Jae Hoon Bahn2,
- Yun Yang2,
- Xianzhi Lin2,
- Stephen Tran3,
- Ei-Wen Yang2,
- Giovanni Quinones-Valdez1 and
- Xinshu Xiao1,2,3,4
- 1Department of Bioengineering,
- 2Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, California 90095, USA;
- 3Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, California 90095, USA;
- 4Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA
Abstract
In eukaryotes, nascent RNA transcripts undergo an intricate series of RNA processing steps to achieve mRNA maturation. RNA editing and alternative splicing are two major RNA processing steps that can introduce significant modifications to the final gene products. By tackling these processes in isolation, recent studies have enabled substantial progress in understanding their global RNA targets and regulatory pathways. However, the interplay between individual steps of RNA processing, an essential aspect of gene regulation, remains poorly understood. By sequencing the RNA of different subcellular fractions, we examined the timing of adenosine-to-inosine (A-to-I) RNA editing and its impact on alternative splicing. We observed that >95% A-to-I RNA editing events occurred in the chromatin-associated RNA prior to polyadenylation. We report about 500 editing sites in the 3′ acceptor sequences that can alter splicing of the associated exons. These exons are highly conserved during evolution and reside in genes with important cellular function. Furthermore, we identified a second class of exons whose splicing is likely modulated by RNA secondary structures that are recognized by the RNA editing machinery. The genome-wide analyses, supported by experimental validations, revealed remarkable interplay between RNA editing and splicing and expanded the repertoire of functional RNA editing sites.
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.231209.117.
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Freely available online through the Genome Research Open Access option.
- Received October 11, 2017.
- Accepted April 26, 2018.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.