Function Of RNA Secondary Structure In Mutually Exclusive Splicing Of Drosophila Dscam Exon 6 Cluster

Alternative splicing is an important processing procedure after RNA transcription in multicellular eukaryotes to increase protein diversity and it has key roles in determining tissue-and species-specific differentiation patterns and in hereditary disease and cancer. Mutually exclusive splicing is one type of alternative splicing, in which only one alternative exon is chosen into mature mRNAs to form different mature mRNAs and eventually to increase protein diversity. As one of the most outstanding cases, Down syndrome cell adhesion molecular (Dscam) can potentially encode 38016 different protein isoforms via alternative splicing of four alternative exon clusters. Although the hypothesis of docking site selector sequence interactions has been verified by our experiments, together with the regulation of LCR on alternative splicing of Dscam, the complex and subtle regulation mechanisms of alternative splicing of Dscam is still to be enriched.In this study, we identified two conserved cis-acting elements in the intron between alternative exon 6.48 and constitutive exon 7 via bioinformatics among 11 kinds of flies. They can pair with each other to form an RNA secondary structure in diverse direction. Mutations, complementary mutation and deletion experiments show that the RNA secondary structure does has a positive regulation of splicing ratio of the exon 6 cluster, not of a specific exon.Besides, the cis-acting element towards constitutive exon 7 may has some binding sites for splicing regulators, which is of great importance to help enrich the regulation mechanisms of mutually exclusive splicing of Dscam exon 6.