Deciphering 3′ss Selection in the Yeast Genome Reveals an RNA Thermosensor that Mediates Alternative Splicing

Meyer, Markus; Plass, Mireya; Pérez-Valle, Jorge; Eyras, Eduardo; Vilardell, Josep

doi:10.1016/j.molcel.2011.07.030

Cited by 108 publications

(151 citation statements)

References 34 publications

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“…Secondary structure has been shown before to play a role in the recognition of some introns by the spliceosome (Deshler and Rossi 1991;Charpentier and Rosbash 1996;Gahura et al 2011;Meyer et al 2011), and structural features have been shown previously to aid in the computational prediction of splice sites (Patterson et al 2002;Marashi et al 2006). However, these computational methods only included information from a predicted optimal structure and did not contemplate a mechanistic hypothesis in the predictive model or the possibility of alternative 39ss selection.…”

Section: Discussionmentioning

confidence: 99%

“…In order to simulate normal growth conditions, we considered the structural properties of the sequence at 22°C (Materials and Methods). The effective distance between the BS and the HAG, calculated by subtracting the number of base positions contained in the optimal secondary structure (Materials and Methods), was not used as a feature to build the classifier but as a filter, as we have shown in a recent work that there is a maximum effective distance beyond which the HAG is never used as a 39ss (Meyer et al 2011; see Supplemental Table S1). …”

Section: Secondary Structures Help Explain 39ss Selectionmentioning

confidence: 99%

“…Interestingly, the structures adopted by the pre-mRNA can be subject to modulation, as changes in RNA polymerase transcription rate or temperature, among others, can affect their formation and stability (Pan and Sosnick 2006;Bevilacqua and Blose 2008;Chen 2008;Mahen et al 2010;Meyer et al 2011) and consequently regulate 39ss selection in yeast. In particular, we have recently described one case where the pre-mRNA secondary structure of one gene is modified by temperature changes, modulating 39ss selection (Meyer et al 2011). Accordingly, we analyzed the impact of temperature changes on 39ss selection at genomic scale using our computational model by comparing 39ss predictions obtained at 22°C with the predictions under heat-shock conditions (37°C).…”

Section: Effects Of Temperature On 39ss Selectionmentioning

confidence: 99%

“…All the considered introns thus contain a canonical 39ss and a BS sequence within 200 nt upstream of the 39ss. In this set, all HAGs (AAG, TAG, and CAG) were collected such that they were located between 10 nt downstream from the BS and the end of the downstream exon, and their effective distance was smaller than 52 nt (see below), as these are the minimum distance and maximum BS-39ss effective distance, respectively, for a 39ss to be recognized (Meyer et al 2011). Additionally, using the SVM described below, we verified that using this effective distance cutoff improves the prediction accuracy (see Supplemental Material).…”

Section: Data Setsmentioning

confidence: 99%

“…In yeast, RNA secondary structures have been shown to influence 59ss recognition by shortening the 59ss-BS distance in yeast (Rogic et al 2008). More recently, a number of cases have been described for which pre-mRNA secondary structure is key for understanding 39ss selection, since it can maintain the 39ss at the right distance from the BS and modulate the accessibility of 39ss to the spliceosome (Gahura et al 2011;Meyer et al 2011). These works have suggested the existence of general rules that would put into context previous findings about the role of RNA structures on 39ss selection (Deshler and Rossi 1991;Goguel et al 1993).…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Secondary Structures Help Explain 39ss Selectionmentioning

confidence: 99%

Section: Effects Of Temperature On 39ss Selectionmentioning

confidence: 99%

Section: Data Setsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Plass¹,

Codony-Servat²,

Ferreira³

et al. 2012

RNA

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Intronic features that determine the selection of the 3′ splice site

Pérez-Valle

Vilardell

2012

WIREs RNA

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Most eukaryotic primary transcripts include segments, or introns, that will be accurately removed during RNA biogenesis. This process, known as pre‐messenger RNA splicing, is catalyzed by the spliceosome, accurately selecting a set of intronic marks from others apparently equivalent. This identification is critical, as incorrectly spliced RNAs can be toxic for the organism. One of these marks, the dinucleotide AG, signals the intronic 3′ end, or 3′ splice site (ss). In this review we will focus on those intronic features that have an impact on 3′ ss selection. These include the location and type of neighboring sequences, and their distance to the 3′ end. We will see that their interplay is needed to select the right intronic end, and that this can be modulated by additional intronic elements that contribute to alternative splicing, whereby diverse RNAs can be generated from identical precursors. This complexity, still poorly understood, is fundamental for the accuracy of gene expression. In addition, a clear knowledge of 3′ ss selection is needed to fully decipher the coding potential of genomes. WIREs RNA 2012 doi: 10.1002/wrna.1131 This article is categorized under: RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Processing > Splicing Regulation/Alternative Splicing Regulatory RNAs/RNAi/Riboswitches > Riboswitches

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RNAs in the spliceosome: Insight from cryoEM structures

et al. 2019

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Pre-mRNA splicing is catalyzed by the spliceosome, a multimegadalton RNAprotein complex. The spliceosome undergoes dramatic compositional and conformational changes through the splicing cycle, forming at least 10 distinct complexes. Recent high-resolution cryoEM structures of various spliceosomal complexes revealed unprecedented details of this large molecular machine. This review highlights insight into the structure and function of the spliceosomal RNA components obtained from these new structures, with a focus on the yeast spliceosome.

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Deciphering 3′ss Selection in the Yeast Genome Reveals an RNA Thermosensor that Mediates Alternative Splicing

Cited by 108 publications

References 34 publications

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

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

Intronic features that determine the selection of the 3′ splice site

RNAs in the spliceosome: Insight from cryoEM structures

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