Computational definition of sequence motifs governing constitutive exon splicing.

By Xiang H. F. Zhang, L. Chasin. Genes & Development, 2004

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We have searched for sequence motifs that contribute to the recognition of human pre-mRNA splice sites by comparing the frequency of 8-mers in internal noncoding exons versus unspliced pseudo exons and 5' untranslated regions (5' untranslated regions [UTRs]) of transcripts of intronless genes. This type of comparison avoids the isolation of sequences that are distinguished by their protein-coding information. We classified sequence families comprising 2069 putative exonic enhancers and 974 putative exonic silencers. Representatives of each class functioned as enhancers or silencers when inserted into a test exon and assayed in transfected mammalian cells. As a class, the enhancer sequencers were more prevalent and the silencer elements less prevalent in all exons compared with introns. A survey of 58 reported exonic splicing mutations showed good agreement between the splicing phenotype and the effect of the mutation on the motifs defined here. The large number of effective sequences implied by these results suggests that sequences that influence splicing may be very abundant in pre-mRNA.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d774df34a64bd749b0bd8f909cd6edb5a8d4fd43

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Citations in the corpus

Learning the sequence determinants of alternative splicing from millions of random sequences. (2015, methodology): “Examples of SREs have been identified computationally by analyzing motif enrichment near splice sites (Castle et al., 2008; Fairbrother et al., 2002; Zhang and Chasin, 2004) or sequence conservation between species (Goren et al., 2006).”
Understanding alternative splicing: towards a cellular code (2005, background): “Recent global analyses have indicated that the relative enrichment in ESEs or ESSs helps to distinguish between authentic exons and pseudo-exon”
Human Splicing Finder: an online bioinformatics tool to predict splicing signals (2009, methodology): “Matrices for splicing enhancers and silencers To maximize the detection of auxiliary motifs, HSF integrated: (i) matrices for SR proteins (SRp40, SC35, SF2/ ASF, SF2/ASF IgM/BRCA1 and SRp55) from the ESE Finder tool (19,27); (ii) sequence motifs shown to be differentially present in exons and intron”
Comparative analysis identifies exonic splicing regulatory sequences--The complex definition of enhancers and silencers. (2006, background): “However, hexamer L7 functions as a strong ESE (Figure 3E, lane 9), suggesting that one out of nine hexamers, not identified so far by this and other studies (Cartegni et al., 2003; Fairbrother et al., 2002; Wang et al., 2004; Zhang and Chasin, 2004 ), may be functional ESRs.”
Alternative splicing: new insights from global analyses. (2006, background): “…provided valuable information Cell 126, July 14, 2006 ©2006 Elsevier Inc. 43 for improving our ability to predict which disease mutations have the potential to disrupt splicing (Cartegni et al., 2002; Fairbrother et al., 2002; Pagani and Baralle, 2004; Wang et al., 2004; Zhang and Chasin, 2004).”
Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. (2008, background): “2002), and by their enrichment in authentic exons versus pseudoexons and 59 UTRs of intronless genes (Zhang and Chasin 2004).”