The effects of alternative splicing on transmembrane proteins in the mouse genome

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Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing 02/2004; DOI: 10.1142/9789812704856_0003
Source: PubMed


Alternative splicing is a major source of variety in mammalian mRNAs, yet many questions remain on its downstream effects on protein function. To this end, we assessed the impact of gene structure and splice variation on signal peptide and transmembrane regions in proteins. Transmembrane proteins perform several key functions in cell signaling and transport, with their function tied closely to their transmembrane architecture. Signal peptides and transmembrane regions both provide key information on protein localization. Thus, any modification to such regions will likely alter protein destination and function. We applied TMHMM and SignalP to a nonredundant set of proteins, and assessed the effects of gene structure and alternative splicing on predicted transmembrane and signal peptide regions. These regions were altered by alternative splicing in roughly half of the cases studied. Transmembrane regions are divided by introns slightly less often than expected given gene structure and transmembrane region size. However, the transmembrane regions in single-pass transmembranes are divided substantially less often than expected. This suggests that intron placement might be subject to some evolutionary pressure to preserve function in these signaling proteins. The data described in this paper is available online at

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Available from: Ron Shigeta
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    • "Alternative splicing is a form of post-and co-transcriptional regulation in which pre-mRNA transcripts from the same gene are spliced in different ways. Alternative splicing can affect any part of a transcript, and it has been well known since the early 2000s that alternative splicing in mammalian genomes frequently remodels conserved or functional motifs in the encoded proteins (Loraine et al., 2002; Cline et al., 2004). These differences can have important functional consequences; in animals as diverse as fruit flies and mammals, differential expression of alternative splice variants supports and enforces cellular differentiation and development. "
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    • "Alternative splicing (AS) can have a biologically relevant effect on protein structure, as it allows the shuffling of protein domains rather than disrupting them [1]. Consequently, alternative splicing can modulate the function of a gene, affecting, for instance, the signal peptides and the transmembrane segments [2,3]. The importance of AS in many genomes has raised the question of its role in the context of evolution. "
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