Efficient 3'-end processing of intron-free G-protein coupled receptor genes. (360G-Wellcome-081083_Z_06_Z)

The open reading frames of most eukaryotic protein encoding genes are interrupted by non-coding sequences. In order to produce a contiguous uninterrupted and translatable messenger RNA, these intervening sequences have to be precisely excised by the splicing apparatus. In recent years, it became evident that the removal of these introns not only results in an mRNA with an uninterrupted ORF but it also affects the efficiency of transcription, 3 -end processing, translation, RNA localisation and d egradation. Given that splicing has such a global effect on all levels of gene expression, it is surprising that more than 5% of mammalian genes do not contain introns. Within the group of intronless genes the family of G-protein coupled receptors are noteworthy because the majority of these important trans-membrane proteins contain intron-free ORFs. This proposal aims to investigate how the melanocortin G-protein coupled receptor genes are efficiently expressed without the stimulatory effect of splicing. In particular we plan to investigate how the 3 -ends of the melanocortin pre-mRNAs are efficiently processed without the enhancing effect of terminal intron removal. We aim to understand the molecular mechanisms that can compensate for the lack of splicing and direct efficient 3 -end formation in this group of genes.