Deletion of Many Yeast Introns Reveals a Minority of Genes that Require Splicing for Function

Parenteau, Julie; Durand, Mathieu; Véronneau, Steeve; Lacombe, Andrée-Anne; Morin, Geneviève; Guérin, Valérie; Cecez, Bojana; Gervais-Bird, Julien; Koh, ChuShin; Brunelle, David; Wellinger, Raymund J.; Chabot, Benoît; Elela, Sherif Abou

doi:10.1091/mbc.e07-12-1254

Cited by 106 publications

(102 citation statements)

References 62 publications

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“…3), which codes for a regulator of mRNA transport (SantosRosa et al 1998). Interestingly, the validated site coincides with one of the alternative 39ss reported before upstream of the open reading frame of MTR2 (Davis et al 2000), which defines an intron that, upon mutation, produces lethality (Parenteau et al 2008). These results confirm that our classifier is able to distinguish real from false 39ss and that it can be used to predict new alternative 39ss.…”

Section: Identification Of Constitutive and Alternative 39ss In 59 Utmentioning

confidence: 52%

RNA secondary structure mediates alternative 3′ss selection in Saccharomyces cerevisiae

Plass¹,

Codony-Servat²,

Ferreira³

et al. 2012

RNA

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Alternative splicing is the mechanism by which different combinations of exons in the pre-mRNA give rise to distinct mature mRNAs. This process is mediated by splicing factors that bind the pre-mRNA and affect the recognition of its splicing signals. Saccharomyces species lack many of the regulatory factors present in metazoans. Accordingly, it is generally assumed that the amount of alternative splicing is limited. However, there is recent compelling evidence that yeast have functional alternative splicing, mainly in response to environmental conditions. We have previously shown that sequence and structure properties of the pre-mRNA could explain the selection of 39 splice sites (ss) in Saccharomyces cerevisiae. In this work, we extend our previous observations to build a computational classifier that explains most of the annotated 39ss in the CDS and 59 UTR of this organism. Moreover, we show that the same rules can explain the selection of alternative 39ss. Experimental validation of a number of predicted alternative 39ss shows that their usage is low compared to annotated 39ss. The majority of these alternative 39ss introduce premature termination codons (PTCs), suggesting a role in expression regulation. Furthermore, a genome-wide analysis of the effect of temperature, followed by experimental validation, yields only a small number of changes, indicating that this type of regulation is not widespread. Our results are consistent with the presence of alternative 39ss selection in yeast mediated by the pre-mRNA structure, which can be responsive to external cues, like temperature, and is possibly related to the control of gene expression.

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Section: Identification Of Constitutive and Alternative 39ss In 59 Utmentioning

confidence: 52%

RNA secondary structure mediates alternative 3′ss selection in Saccharomyces cerevisiae

Plass¹,

Codony-Servat²,

Ferreira³

et al. 2012

RNA

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“…Indeed, introns have been shown to increase the fitness of yeast in two ways: (1) regulated splicing posttranscriptionally regulates gene expression (Engebrecht et al 1991;Li et al 1996;Nakagawa and Ogawa 1999;Preker et al 2002;Juneau et al 2007;Parenteau et al 2008) and (2) introns can function to enhance the transcriptional and translational output of the genes they occupy ( Juneau et al 2006). Here we provide compelling evidence that introns also improve the fitness of yeast by increasing protein diversity through alternative splicing.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, all 13 meiosis-specific introncontaining genes are regulated post-transcriptionally with splicing repressed during vegetative growth and induced during sporulation (Engebrecht et al 1991;Nakagawa and Ogawa 1999;Juneau et al 2007). Other examples of regulated splicing include YRA1 and MTR2 (RNA export) (Preker et al 2002;Parenteau et al 2008) and RPL30 (ribosomal) (Li et al 1996).…”

mentioning

confidence: 99%

Alternative Splicing of PTC7 inSaccharomyces cerevisiaeDetermines Protein Localization

2009

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It is well established that higher eukaryotes use alternative splicing to increase proteome complexity. In contrast, Saccharomyces cerevisiae, a single-cell eukaryote, conducts predominantly regulated splicing through retention of nonfunctional introns. In this article we describe our discovery of a functional intron in the PTC7 (YHR076W) gene that can be alternatively spliced to create two mRNAs that code for distinct proteins. These two proteins localize to different cellular compartments and have distinct cellular roles. The protein translated from the spliced mRNA localizes to the mitochondria and its expression is carbon-source dependent. In comparison, the protein translated from the unspliced mRNA contains a transmembrane domain, localizes to the nuclear envelope, and mediates the toxic effects of Latrunculin A exposure. In conclusion, we identified a definitive example of functional alternative splicing in S. cerevisiae that confers a measurable fitness benefit. I N higher eukaryotes alternative splicing is pervasive; in humans the majority of genes are alternatively spliced to form multiple proteins (Modrek et al. 2001;Johnson et al. 2003). In contrast, only 5% of the genes in Saccharomyces cerevisiae contain introns and .95% of those intron-containing genes possess only a single intron (Nash et al. 2007). The simple architecture of the yeast genome constrains its ability to utilize alternative splicing and has encouraged the view that alternative splicing is absent in S. cerevisiae. Currently no conclusive examples of functional alternative splicing exist; most confirmed instances of alternative splicing in yeast downregulate gene expression, a process that is often referred to as ''regulated splicing.'' In this process, nonfunctional introns are not spliced out of the transcript and premature stop codons are included in the fully processed mRNA. The stop codons activate the nonsense-mediated decay (NMD) pathway and the mRNA is degraded before it can be translated (Gonzalez et al. 2001).The transition from vegetative growth to meiosis illustrates how regulated splicing improves yeast fitness. DNA breakage and recombination could be toxic during vegetative growth, and therefore entrance into meiosis is tightly controlled. Consequently, all 13 meiosis-specific introncontaining genes are regulated post-transcriptionally with splicing repressed during vegetative growth and induced during sporulation (Engebrecht et al. 1991;Nakagawa and Ogawa 1999;Juneau et al. 2007). Other examples of regulated splicing include YRA1 and MTR2 (RNA export) (Preker et al. 2002;Parenteau et al. 2008) and RPL30 (ribosomal) (Li et al. 1996).In contrast to regulated splicing, there is only one example in S. cerevisiae where splicing results in the expression of multiple proteins, SRC1 (Grund et al. 2008). SRC1 contains a single intron located at the 39 end of the pre-mRNA. The intron has two alternative 59-splice sites (Rodriguez-Navarro et al. 2002). Splicing at the most highly conserved 59-splice site (Bon et al. 2003) ...

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“…Indeed, 90 bp is about the distance that would allow a gene to change from bi-stable to crystal chromatin state (and vice versa). Unfortunately, when using our model to compute the nucleosome occupancy profiles on introncontaining intragenic sequences with and after removing the intron (Parenteau et al 2008), the sampling of each category (crystal, bi-stable, other) was too small to draw significant conclusions. An alternative hypothesis relies on recent studies indicating that splicing regulation might be associated with chromatin-mediated regulation of transcriptional elongation, involving the action of remodeling factors, such as Swi/Snf (Kornblihtt 2006;Allemand et al 2008).…”

Section: Proof Onlymentioning

confidence: 99%

Thermodynamics of Intragenic Nucleosome Ordering

et al. 2009

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Numerous AU2studies of chromatin structure showed that nucleosome free regions (NFRs) located at 59 gene ends contribute to transcription initiation regulation. Here, we determine the role of intragenic chromatin structure on gene expression regulation. We show that, along Saccharomyces cerevisiae genes, nucleosomes are highly organized following two types of architecture that depend only on the distance between the NFRs located at the 59 and 39 gene ends. In the first type, this distance constrains in vivo the positioning of n nucleosomes regularly organized in a ''crystal-like'' array. In the second type, this distance is such that the corresponding genes can accommodate either n or (n + 1) nucleosomes, thereby displaying two possible crystal-like arrays of n weakly compacted or n + 1 highly compacted nucleosomes. This adaptability confers ''bistable'' properties to chromatin and is a key to its dynamics. Compared to crystal-like genes, bi-stable genes present higher transcriptional plasticity, higher sensitivity to chromatin regulators, higher H3 turnover rate, and lower H2A.Z enrichment. The results strongly suggest that transcription elongation is facilitated by higher chromatin compaction. The data allow us to propose a new paradigm of transcriptional control mediated by the stability and the level of compaction of the intragenic chromatin architecture and open new ways for investigating eukaryotic gene expression regulation.

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Deletion of Many Yeast Introns Reveals a Minority of Genes that Require Splicing for Function

Cited by 106 publications

References 62 publications

RNA secondary structure mediates alternative 3′ss selection in Saccharomyces cerevisiae

RNA secondary structure mediates alternative 3′ss selection in Saccharomyces cerevisiae

Alternative Splicing of PTC7 inSaccharomyces cerevisiaeDetermines Protein Localization

Thermodynamics of Intragenic Nucleosome Ordering

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