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Evolution of intron splicing towards optimized gene expression is based on various Cis- and Trans-molecular mechanisms

dc.contributor.authorFrumkin, Idan
dc.contributor.authorYofe, Ido
dc.contributor.authorBar-Ziv, Raz
dc.contributor.authorGurvich, Yonat
dc.contributor.authorLu, Yen-Yun
dc.contributor.authorVoichek, Yoav
dc.contributor.authorTowers, Ruth
dc.contributor.authorSchirman, Dvir
dc.contributor.authorKrebber, Heike
dc.contributor.authorPilpel, Yitzhak
dc.date.accessioned2019-10-01T11:11:54Z
dc.date.available2019-10-01T11:11:54Z
dc.date.issued2019de
dc.identifier.urihttp://resolver.sub.uni-goettingen.de/purl?gs-1/16463
dc.description.abstractSplicing expands, reshapes, and regulates the transcriptome of eukaryotic organisms. Despite its importance, key questions remain unanswered, including the following: Can splicing evolve when organisms adapt to new challenges? How does evolution optimize inefficiency of introns' splicing and of the splicing machinery? To explore these questions, we evolved yeast cells that were engineered to contain an inefficiently spliced intron inside a gene whose protein product was under selection for an increased expression level. We identified a combination of mutations in Cis (within the gene of interest) and in Trans (in mRNA-maturation machinery). Surprisingly, the mutations in Cis resided outside of known intronic functional sites and improved the intron's splicing efficiency potentially by easing tight mRNA structures. One of these mutations hampered a protein's domain that was not under selection, demonstrating the evolutionary flexibility of multi-domain proteins as one domain functionality was improved at the expense of the other domain. The Trans adaptations resided in two proteins, Npl3 and Gbp2, that bind pre-mRNAs and are central to their maturation. Interestingly, these mutations either increased or decreased the affinity of these proteins to mRNA, presumably allowing faster spliceosome recruitment or increased time before degradation of the pre-mRNAs, respectively. Altogether, our work reveals various mechanistic pathways toward optimizations of intron splicing to ultimately adapt gene expression patterns to novel demands.de
dc.language.isoengde
dc.rightsopenAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectIntrons; Mutation; Evolutionary adaptation; Gene expression; Evolutionary genetics; RNA splicing; Messenger RNA; Point mutationde
dc.subject.ddc572
dc.titleEvolution of intron splicing towards optimized gene expression is based on various Cis- and Trans-molecular mechanismsde
dc.typejournalArticlede
dc.identifier.doi10.1371/journal.pbio.3000423
dc.identifier.doi10.1371/journal.pbio.3000423.g001
dc.identifier.doi10.1371/journal.pbio.3000423.g002
dc.identifier.doi10.1371/journal.pbio.3000423.g003
dc.identifier.doi10.1371/journal.pbio.3000423.g004
dc.identifier.doi10.1371/journal.pbio.3000423.g005
dc.identifier.doi10.1371/journal.pbio.3000423.g006
dc.identifier.doi10.1371/journal.pbio.3000423.g007
dc.identifier.doi10.1371/journal.pbio.3000423.s001
dc.identifier.doi10.1371/journal.pbio.3000423.s002
dc.identifier.doi10.1371/journal.pbio.3000423.s003
dc.identifier.doi10.1371/journal.pbio.3000423.s004
dc.type.versionpublishedVersionde
dc.relation.eISSN1545-7885
dc.bibliographicCitation.volume17de
dc.bibliographicCitation.issue8de
dc.type.subtypejournalArticle
dc.identifier.pmid31442222
dc.bibliographicCitation.articlenumbere3000423de
dc.description.statuspeerReviewedde
dc.bibliographicCitation.journalPLOS Biologyde


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