Origin of introns by ‘intronization’ of exonic sequences

Irimia, Manuel; Rukov, Jakob Lewin; Penny, David; Vinther, Jeppe; Garcia‐Fernàndez, Jordi; Roy, Scott William

doi:10.1016/j.tig.2008.05.007

Cited by 74 publications

(81 citation statements)

References 30 publications

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“…Indeed, we found IRs in the mammalian-specific genes human CCKBR, CD55, and FMNL1 and mouse Tgif2 that qualified as exitrons (Supplemental Table 15). Moreover, additional cases of splicing of intraexonic sequences were described in Caenorhabditis elegans, and a hypothesis on their origin was proposed (see below) (Irimia et al 2008). Altogether, these findings demonstrate that EIS is a common strategy to increase transcriptome diversity in plant and nonplant species.…”

Section: Constitutive Introns Exitron Exons Constitutive Exons Retainmentioning

confidence: 82%

Unmasking alternative splicing inside protein-coding exons defines exitrons and their role in proteome plasticity

et al. 2015

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Alternative splicing (AS) diversifies transcriptomes and proteomes and is widely recognized as a key mechanism for regulating gene expression. Previously, in an analysis of intron retention events in Arabidopsis, we found unusual AS events inside annotated protein-coding exons. Here, we also identify such AS events in human and use these two sets to analyse their features, regulation, functional impact, and evolutionary origin. As these events involve introns with features of both introns and protein-coding exons, we name them exitrons (exonic introns). Though exitrons were detected as a subset of retained introns, they are clearly distinguishable, and their splicing results in transcripts with different fates. About half of the 1002 Arabidopsis and 923 human exitrons have sizes of multiples of 3 nucleotides (nt). Splicing of these exitrons results in internally deleted proteins and affects protein domains, disordered regions, and various post-translational modification sites, thus broadly impacting protein function. Exitron splicing is regulated across tissues, in response to stress and in carcinogenesis. Intriguingly, annotated intronless genes can be also alternatively spliced via exitron usage. We demonstrate that at least some exitrons originate from ancestral coding exons. Based on our findings, we propose a "splicing memory" hypothesis whereby upon intron loss imprints of former exon borders defined by vestigial splicing regulatory elements could drive the evolution of exitron splicing. Altogether, our studies show that exitron splicing is a conserved strategy for increasing proteome plasticity in plants and animals, complementing the repertoire of AS events.

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Section: Constitutive Introns Exitron Exons Constitutive Exons Retainmentioning

confidence: 82%

Unmasking alternative splicing inside protein-coding exons defines exitrons and their role in proteome plasticity

et al. 2015

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“…A very few spliceosomal introns are known to derive from mobile elements in plant, fly, and human (33)(34)(35)(36)(37). In C. elegans, a few de novo introns are thought to have originated from internal exonic sequences, with their splice sites created by point mutations (19). In human, de novo introns have been reported in isolated cases to result from fortuitous splicesite creation (38,39).…”

Section: Novel Splice Sites Can Be Activated From Latent Sites After mentioning

confidence: 99%

“…Although the sources of spliceosomal introns remain a mystery, several models have been proposed for their origin (17)(18)(19): (i) recruitment from an ancestral pool of group-II introns, with the current intron set representing the remnants of a large ancestral pool, (ii) insertion of preexisting spliced introns into genes through RNA and cDNA intermediates, (iii) insertion and decay of transposons, (iv) internal tandem duplication of coding sequences containing AGGT cryptic splice sites, (v) emergence from genomic regions that are subject to posttranscriptional surveillance pathways, and (vi) generation of novel splice sites by point mutations in coding regions. However, these hypotheses either have few examples to support them or have not been tested, and to date, the mechanisms of intron creation remain puzzling and controversial (20)(21)(22).…”

mentioning

confidence: 99%

Ubiquitous internal gene duplication and intron creation in eukaryotes

Gao

Lynch

2009

Proc. Natl. Acad. Sci. U.S.A.

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Duplication of genomic segments provides a primary resource for the origin of evolutionary novelties. However, most previous studies have focused on duplications of complete protein-coding genes, whereas little is known about the significance of duplication segments that are entirely internal to genes. Our examination of six fully sequenced genomes reveals that internal duplications of gene segments occur at a high frequency (0.001-0.013 duplications/gene per million years), similar to that of complete gene duplications, such that 8 -17% of the genes in a genome carry duplicated intronic and/or exonic regions. At least 7-30% of such genes have acquired novel introns, either because a prior intron in the same gene has been duplicated, or more commonly, because a spatial change has activated a latent splice site. These results strongly suggest a major evolutionary role for internal gene duplications in the origin of genomic novelties, particularly as a mechanism for intron gain.exons ͉ genome evolution ͉ intron evolution ͉ splice site

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“…Type A are ancestral introns flanked by constitutive exons; Type B arose by ''intronization'' of ancestral exonic sequence (Irimia et al 2008); and Type C are located adjacent to one or more alternative exons that may or may not be conserved between species.…”

Section: Assignment Of Retained Intron Typesmentioning

confidence: 99%

Widespread intron retention in mammals functionally tunes transcriptomes

et al. 2014

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Alternative splicing (AS) of precursor RNAs is responsible for greatly expanding the regulatory and functional capacity of eukaryotic genomes. Of the different classes of AS, intron retention (IR) is the least well understood. In plants and unicellular eukaryotes, IR is the most common form of AS, whereas in animals, it is thought to represent the least prevalent form. Using high-coverage poly(A)+ RNA-seq data, we observe that IR is surprisingly frequent in mammals, affecting transcripts from as many as three-quarters of multiexonic genes. A highly correlated set of cis features comprising an ''IR code'' reliably discriminates retained from constitutively spliced introns. We show that IR acts widely to reduce the levels of transcripts that are less or not required for the physiology of the cell or tissue type in which they are detected. This ''transcriptome tuning'' function of IR acts through both nonsense-mediated mRNA decay and nuclear sequestration and turnover of IR transcripts. We further show that IR is linked to a cross-talk mechanism involving localized stalling of RNA polymerase II (Pol II) and reduced availability of spliceosomal components. Collectively, the results implicate a global checkpoint-type mechanism whereby reduced recruitment of splicing components coupled to Pol II pausing underlies widespread IR-mediated suppression of inappropriately expressed transcripts.

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Origin of introns by ‘intronization’ of exonic sequences

Cited by 74 publications

References 30 publications

Unmasking alternative splicing inside protein-coding exons defines exitrons and their role in proteome plasticity

Unmasking alternative splicing inside protein-coding exons defines exitrons and their role in proteome plasticity

Ubiquitous internal gene duplication and intron creation in eukaryotes

Widespread intron retention in mammals functionally tunes transcriptomes

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