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

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. © 2012 John Wiley & Sons, Ltd.Work in JV's laboratory is supported by the Spanish Ministry of Science (BIO2008-01091 and 2011-25697) and CSIC (200920I195).Peer Reviewe

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

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. © 2012 John Wiley & Sons, Ltd.Work in JV's laboratory is supported by the Spanish Ministry of Science (BIO2008-01091 and 2011-25697) and CSIC (200920I195).Peer Reviewe