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Open AccessArticle

An Evolutionary Mechanism for the Generation of Competing RNA Structures Associated with Mutually Exclusive Exons

1
Skolkovo Institute for Science and Technology, Ulitsa Nobelya 3, Moscow 121205, Russia
2
Faculty of Bioengineering and Bioinformatics, Moscow State University 1-73, Moscow 119899, Russia
3
Faculty of Computer Science, Higher School of Economics, Kochnovskiy Proyezd 3, Moscow 125319, Russia
*
Author to whom correspondence should be addressed.
Genes 2018, 9(7), 356; https://doi.org/10.3390/genes9070356
Received: 10 May 2018 / Revised: 6 July 2018 / Accepted: 13 July 2018 / Published: 17 July 2018
(This article belongs to the Special Issue Computational Analysis of RNA Structure and Function)
Alternative splicing is a commonly-used mechanism of diversifying gene products. Mutually exclusive exons (MXE) represent a particular type of alternative splicing, in which one and only one exon from an array is included in the mature RNA. A number of genes with MXE do so by using a mechanism that depends on RNA structure. Transcripts of these genes contain multiple sites called selector sequences that are all complementary to a regulatory element called the docking site; only one of the competing base pairings can form at a time, which exposes one exon from the cluster to the spliceosome. MXE tend to have similar lengths and sequence content and are believed to originate through tandem genomic duplications. Here, we report that pre-mRNAs of this class of exons have an increased capacity to fold into competing secondary structures. We propose an evolutionary mechanism for the generation of such structures via duplications that affect not only exons, but also their adjacent introns with stem-loop structures. If one of the two arms of a stem-loop is duplicated, it will generate two selector sequences that compete for the same docking site, a pattern that is associated with MXE splicing. A similar partial duplication of two independent stem-loops produces a pattern that is consistent with the so-called bidirectional pairing model. These models explain why tandem exon duplications frequently result in mutually exclusive splicing. View Full-Text
Keywords: mutually exclusive exons; alternative splicing; RNA structure; long-range; duplication; competing structures; evolution; bidirectional control; Dscam; srp mutually exclusive exons; alternative splicing; RNA structure; long-range; duplication; competing structures; evolution; bidirectional control; Dscam; srp
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MDPI and ACS Style

Ivanov, T.M.; Pervouchine, D.D. An Evolutionary Mechanism for the Generation of Competing RNA Structures Associated with Mutually Exclusive Exons. Genes 2018, 9, 356. https://doi.org/10.3390/genes9070356

AMA Style

Ivanov TM, Pervouchine DD. An Evolutionary Mechanism for the Generation of Competing RNA Structures Associated with Mutually Exclusive Exons. Genes. 2018; 9(7):356. https://doi.org/10.3390/genes9070356

Chicago/Turabian Style

Ivanov, Timofei M.; Pervouchine, Dmitri D. 2018. "An Evolutionary Mechanism for the Generation of Competing RNA Structures Associated with Mutually Exclusive Exons" Genes 9, no. 7: 356. https://doi.org/10.3390/genes9070356

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