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

Genes
Timofei M Ivanov, Dmitri D Pervouchine

Abstract

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 indep...Continue Reading

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Citations

Sep 16, 2020·Wiley Interdisciplinary Reviews. RNA·Bingbing XuYongfeng Jin
Jul 28, 2020·International Journal of Molecular Sciences·Katarzyna Taylor, Krzysztof Sobczak
Dec 18, 2020·Nucleic Acids Research·Marina KalininaDmitri D Pervouchine
Feb 8, 2021·Nucleic Acids Research·Jana KrálovičováIgor Vořechovský

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Software Mentioned

RNAplex
phylo
intersectBed
UCSC Genome Browser
Biopython
ggplot2
bedtools getfasta
GENCODE
RNAup
pairwise2

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