Researchers say that the SNPs found in individuals with extreme BMI that do not alter protein sequence information alter mRNA splicing.
SNPs have previously been thought to produce changes in the protein sequence encoded by a gene (nonsynonymous SNPs). Studies have indicated, however, that a significant number of SNPs do not alter the predicted protein sequence (synonymous SNPs), suggesting that other regulatory mechanisms might be influenced.
In the current work, researchers analyzed a newly described dataset of SNPs found in individuals with extreme BMI values. Nearly 40% of the SNPs associated with obesity do not alter the protein-coding sequence of genes, they report.
The team found that synonymous SNPs associated with extreme BMI are located near splice sites in exons and exhibit a tendency to reside within splicing regulatory regions. They suggest that these SNPs could alter the normal splicing pattern. Furthermore, it was discovered that the exons harboring these SNPs exhibit weak splice sites, indicating that they could be prone to reduced frequency of splicing, potentially disrupting function of the translated protein, according to the investigators.
“When a certain exon is added only to a fraction of the mRNA molecules and not the others, the mRNA molecules without the exon cannot support proper protein synthesis and the overall level of required protein is reduced,” describes colead author Eddo Kim from Tel-Aviv University.
The research involved investigators from Tel-Aviv University and the University of California, San Francisco. This study was published online on December 20 in Genome Research.