CA-repeat enhancer

Simple dinucleotide repeats are commonly found throughout the human genome, but their functional significance has been unclear. In an Advanced Online Publication in Nature Structural Biology, Jingyi Hui and colleagues describe an unusual role for a CA-repeat in regulating mRNA splicing (Nature Structural Biology, doi:10.1038/nsb875, 25 November 2002).

The human endothelial nitric oxide synthase (eNOS) gene contains a polymorphic CA repeat, (CA)_14-44, in intron 13 that has been linked to a risk for coronary artery diseases. The intronic repeat was necessary for eNOS gene splicing in vitro and in vivo, and splicing efficiency correlated with the number of repeats. Biotinylated CA-repeats were used to affinity-purify a repeat-binding protein, identified as hnRNP L (heterogenous nuclear ribonucleoprotein L). The hnRNP L protein specifically activated eNOS splicing.

These results suggest that CA repeats and hnRNP L may regulate the splicing of other genes containing intronic polymorphic repeats.