Regulation of tissue-specific alternative splicing: exon-specific cis-elements govern the splicing of leukocyte common antigen pre-mRNA.

Open Access
Publisher Website
Google Scholar
Abstract
Tissue‐specific alternative splicing is an important mechanism for controlling gene expression. Exons 4, 5 and 6 of the human leukocyte common antigen (LCA) gene are included in B cell mRNA but excluded from thymocyte mRNA by differential splicing. In order to study this tissue‐specific alternative splicing, we constructed mini‐genes that contain only a few of the LCA exons and the SV40 promoter. Mouse B cells and thymocytes were transfected with these mini‐gene constructs and the structures of mRNAs were determined by primer extension analysis. The results show that the same primary transcript is spliced alternatively in B cells and thymocytes. This finding suggests that there is a tissue‐specific trans‐acting factor that regulates the alternative splicing of LCA pre‐mRNA. By making various deletion mutants, cis‐elements necessary for tissue‐specific splicing were confined within the alternatively spliced exons and their immediate flanking intron sequences. Furthermore, linker scanning analysis shows that there are at least three distinct cis‐elements within the LCA exon 4 sequence that are required for tissue‐specific alternative splicing. Possible mechanisms of LCA alternative splicing are discussed.