Adult forms of the Ca2+ATPase of sarcoplasmic reticulum. Expression in developing skeletal muscle.

Abstract

Two separate genes encode fast-twitch and slow-twitch/cardiac muscle forms of the Ca2+ ATPase of sarcoplasmic reticulum. Full length Ca2+ ATPase clones have been isolated from adult rabbit fast-twitch, slow-twitch, and cardiac muscles. Segments of these clones containing unique sequences have been used as probes to study developmental changes in Ca2+ ATPase transcripts. The fast-twitch Ca2+ ATPase transcript undergoes developmentally regulated alternative splicing in which a penultimate 42-base pair exon is retained in the adult transcript but is excised in the neonatal transcript. This additional exon shifts the exon encoding the neonatal carboxyl-terminal sequence, -Asp-Pro-Glu-Asp-Glu-Arg-Arg-Lys (Brandl, C. J., Green, N. M., Korczak, B., and MacLennan, D. H. (1986) Cell 44, 597-607) into a nontranslated region and results in the expression of an adult isoform with a carboxyl-terminal -Gly. The neonatal form of the fast-twitch Ca2+ ATPase represents 72% of the fast-twitch Ca2+ ATPase transcripts just prior to birth but only 17% by 14 days of age and 4% in adult fast-twitch muscle. Adult slow-twitch, adult cardiac, and neonatal skeletal muscles express an identical Ca2+ATPase mRNA transcript which is distinct from either of the fast-twitch forms. The slow-twitch/cardiac Ca2+ ATPase is the predominant form expressed in late fetal and early neonatal rabbit skeletal muscle, but this form is lost as the skeletal muscle differentiates into a fast-twitch state. Three or more alternative polyadenylation signals exist for this mRNA in all tissues with the most 3' signal predominating.