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

Abstract

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

Nucleotide sequence composition adjacent to intronic splice sites improves splicing efficiency via its effect on pre-mRNA local folding in fungi

“…Some previous studies have investigated the efficiency of splicing either for a specific intron or systematically for all introns, and under a variety of environmental conditions or in varying genetic backgrounds (Pleiss et al 2007;Bergkessel et al 2011;Pérez-Valle and Vilardell 2012). Such studies have demonstrated that different introns exhibit a large range of SEs under varying conditions and have diverse proteinaceous requirements (Clark et al 2002).…”

An intronic RNA structure modulates expression of the mRNA biogenesis factor Sus1

“…3A). This mutant had 18 nt less relative to wild-type I2, but all intronic features relevant for splicing were well within functional range: the total size of the mutant intron was 52 nt (the minimum size has been proposed to be 50 nt), the distance between the 5 ′ SS and the BS was 28 nt (greater than the required 25 nt minimum), and there were 12 nt between the BS and the 3 ′ SS (10 nt are necessary in this case as a minimum) (Meyer et al 2011;Pérez-Valle and Vilardell 2012). To evaluate the expression efficiency of this mutant in vivo, we used the CUP1 reporter system (Lesser and Guthrie 1993).…”

“…The UV-thermal denaturation experiments showed that this intron 2 hairpin had surprisingly low thermal stability. It is well established that both the BS and the PPT of the introns need to be single-stranded to allow binding of the BBP (SF1 in mammals) and Mud2 (U2AF 65 ) proteins in the first steps of spliceosome assembly (Gahura et al 2011;Pérez-Valle and Vilardell 2012). It is therefore remarkable that two of the BS nucleotides (A 45 and C 46 ) and the complete PPT of I2 are contained in the base-paired stem of the I2 hairpin.…”

“…For example, in the case of splicing intron RNA folding has been shown to influence 3 ′ SS selection through the masking of AG sequences inside double-helical stems, or by bringing BS and 3 ′ SS sequences into functional proximity (Deshler and Rossi 1991;Rogic et al 2008;Warf and Berglund 2010;Meyer et al 2011;Pérez-Valle and Vilardell 2012). In S. cerevisiae, intronic RNA structures have been reported to play a role in autoregulating RPL30 and YRA1 expression at different levels (Dong et al 2010;Meyer et al 2011).…”

IDENTIFICATION OF RNA STRUCTURES MODULATING THE EXPRESSION OF THE mRNA BIOGENESIS FACTOR SUS1

“…This is usually accomplished by modulation of the accessibility or spatial distribution of splicing signal sequences via base-pairing [76] but also through the presence of more complex folds like riboswitches and ribozymes [77]- [80]. In yeast, for example, the RP51B gene contains a predicted stem-loop that brings the 5' and 3' splice sites into closer proximity.…”