Identification of a new SERCA2 splice variant regulated during monocytic differentiation

Sarco/endoplasmic reticulum-type calcium transport ATPases (SERCA enzymes) pump calcium ions from the cytosol into the endoplasmic reticulum. We report that in addition to the ubiquitously expressed SERCA2b isoform, a new splice variant of SERCA2 can be detected (SERCA2c) that arises from the inclusion of a short intronic sequence located between exons 20 and 21 of the SERCA2a isoform. Sequence analysis revealed classical splice donor and acceptor sites, as well as a branch-point site. Due to the presence in the new exon of an in-frame stop codon that is preceded by a 17 bp coding sequence, this mRNA potentially codes for a protein with a truncated C-terminus containing a short unique C-terminal peptide stretch. SERCA2c message was detected in epithelial, mesenchymal, and hematopoietic cell lines, as well as in primary human monocytes. Moreover, we found that during monocytic differentiation total SERCA2 ATPase expression is induced on the protein and mRNA level and that the novel SERCA2c messenger is also up-regulated during this process. These data indicate that the alternative splicing pattern of the 3(') region of the SERCA2 primary transcript is more complex than that previously thought and that this enzyme may be involved in the process of monocyte differentiation.