Most eukaryotic protein-coding genes are split into exons and introns, and introns need to be spliced for the production of mature mRNA by pre-mRNA splicing. Pre-mRNA splicing is very important for eukaryotic gene expression, because it is not only a key step in producing mature mRNA, but can also affect transcription and translation. The purpose of this study is to investigate the relationship between gene expression and splicing efficiency since the relationship has not been studied systematically from a bioinformatic approach. In this thesis research, we focus on the question of how gene expression would constrain the evolution of three principal splicing signals: the donor splice site, the acceptor splice site, and the branchpoint sequence (BPS).
We chose yeast, Saccharomyces cerevisiae, as the model organism in this study due to its many research advantages such as relatively simple splicing mechanism and extensive genome-wide characterization of gene expression at both transcript and protein levels. We first studied the relationship between gene expression and the strength of the donor and acceptor splice sites in the yeast, with the latter being characterized by position weight matrix scores. We found that donor and acceptor splice sites in highly expressed genes have significantly higher mean, but smaller variance, of splicing strength than that in lowly expressed genes. In addition, genes with extremely low splice site strength tend to be spliced by non-spliceosomal mechanisms, and the last nucleotide on the exon side in the donor splice site (immediately upstream of the 5'GU dinucleotide) is important for splicing. We further studied the relationship between gene expression and BPS in the yeast. The results revealed that the BPS strength of highly expressed yeast intron-containing genes (ICGs) is significantly higher than that of lowly expressed yeast ICGs. Moreover, highly expressed yeast ICGs have significantly longer distance between the donor splice site and BPS (Si distance) and slightly longer distance between BPS and the acceptor splice site (S2 distance) than lowly expressed yeast ICGs. The long Si distance of highly expressed yeast ICG does not indicate the potential of enhancing splicing efficiency through forming secondary structure in the region between the donor splice site and BPS.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/27801 |
| Date | January 2008 |
| Creators | Ma, Pinchao |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 64 p. |
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