Article

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

Affymetrix Inc., 6550 Vallejo Street, Suite 100, Emeryville, CA 94608, USA.
Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing 02/2004; DOI: 10.1142/9789812704856_0003
Source: PubMed

ABSTRACT 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 http://www.affymetrix.com/community/publications/affymetrix/tmsplice/.

0 Followers
 · 
87 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alternative splicing enables a single gene to produce multiple mRNA isoforms by varying splice site selection. In animals, alternative splicing of mRNA isoforms between cell types is widespread and supports cellular differentiation. In plants, at least 20% of multi-exon genes are alternatively spliced, but the extent and significance of tissue-specific splicing is less well understood, partly because it is difficult to isolate cells of a single type. Pollen is a useful model system to study tissue-specific splicing in higher plants because pollen grains contain only two cell types and can be collected in large amounts without damaging cells. Previously, we identified pollen-specific splicing patterns by comparing RNA-Seq data from Arabidopsis pollen and leaves. Here, we used semi-quantitative PCR to validate pollen-specific splicing patterns among genes where RNA-Seq data analysis indicated splicing was most different between pollen and leaves. PCR testing confirmed eight of nine alternative splicing patterns, and results from the ninth were inconclusive. In four genes, alternative transcriptional start sites coincided with alternative splicing. This study highlights the value of the low-cost PCR assay as a method of validating RNA-Seq results.
    04/2015; 3. DOI:10.7717/peerj.919
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alternative splicing is now commonly thought to affect more than half of all human genes. Recent studies have investigated not only the scope but also the biological impact of alternative splicing on a large scale, revealing that its role in generating proteome diversity may be augmented by a role in regulation. For instance, protein function can be regulated by the removal of interaction or localization domains by alternative splicing. Alternative splicing can also regulate gene expression by splicing transcripts into unproductive mRNAs targeted for degradation. To fully understand the scope of alternative splicing, we must also determine how many of the predicted splice variants represent functional forms. Comparisons of alternative splicing between human and mouse genes show that predominant splice variants are usually conserved, but rare variants are less commonly shared. Evolutionary conservation of splicing patterns suggests functional importance and provides insight into the evolutionary history of alternative splicing.
    Current Opinion in Structural Biology 05/2004; DOI:10.1016/S0959-440X(04)00076-4 · 8.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alternative splicing is now recognized as a major mechanism for transcriptome and proteome diversity in higher eukaryotes. Yet, its evolution is poorly understood. Most studies focus on the evolution of exons and introns at the gene level, while only few consider the evolution of transcripts. In this paper, we present a framework for transcript phylogenies where ancestral transcripts evolve along the gene tree by gains, losses, and mutation. We demonstrate the usefulness of our method on a set of 805 genes and two different topics. First, we improve a method for transcriptome reconstruction from ESTs (ASPic), then we study the evolution of function in transcripts. The use of transcript phylogenies allows us to double the specificity of ASPic, whereas results on the functional study reveal that conserved transcripts are more likely to share protein domains than functional sites. These studies validate our framework for the study of evolution in large collections of organisms from the perspective of transcripts; for this purpose, we developed and provide a new tool, TrEvoR.
    IEEE/ACM Transactions on Computational Biology and Bioinformatics 11/2012; DOI:10.1109/TCBB.2012.145 · 1.54 Impact Factor

Full-text (2 Sources)

Download
41 Downloads
Available from
May 22, 2014