Divergent mechanisms in generating molecular variations of alphaRYR and betaRYR in turkey skeletal muscle.

(1) Molecular variations in two turkey skeletal muscle ryanodine receptor gene isoforms, alphaRYR and betaRYR, were analyzed by cloning and sequencing the entire cDNAs of the two isoforms. (2) Ten alternative splicing transcript variants (ASTVs) in the alphaRYR isoform were identified. These variants were clustered in three alternative splicing regions (ASRs). Two ASRs overlap with the divergent regions (DRs) of the two isoforms. Only four ASTVs did not contain a frame shift and potentially can be translated into alphaRYR channel proteins. The expression of these three ASTVs was developmentally or environmentally regulated. (3) Ten SNPs and eight haplotypes, divergent in the ten SNP positions, were identified in betaRYR. Although the ten SNPs were synonymous, different mRNA secondary structures of betaRYR and different stability of the structures were predicted for several SNPs. (4) The intriguing finding of this study is that alphaRYR and betaRYR use completely divergent mechanisms to generate molecular variations. Alternative splicing generates ASTVs of alphaRYR, whereas the presence of SNPs may change the secondary mRNA structure of betaRYR. These divergent mechanisms could affect calcium channel activity of either or both RYR isoforms.