Human CKIα L and CKIα S are encoded by both 2.4- and 4.2-kb transcripts, the longer containing multiple RNA-destablising elements

Abstract

Casein kinase I (CKI) are a family of conserved second messenger-independent serine/threonine protein kinases found in all eukaryotes. The avian and mammalian CKI alpha isoform has four splice variants differing in the presence or absence of 28 amino acids (‘ L’ insertion) in the catalytic domain and/or 12 amino acids (‘ S’ insertion) in the regulatory domain. Here we report the isolation of cDNAs encoding human CKIα L and CKIα S. We find human CKIα L has a preference to phosphorylate phosvitin over casein, with a higher K m for casein than phosvitin, the reverse being the case for human CKIα S. Both human CKIα L, and CKIα S are derived from 4.2-kb mRNA transcripts and 2.4-kb transcripts, the latter probably generated by use of an alternate polyadenylation signal identified in the longer transcripts. The 4.2-kb transcripts contain six RNA-destabilising AU-rich element (ARE) motifs in the 3′-untranslated region (UTR), while the 2.4-kb transcripts contain a single ARE motif. In vitro analysis of CKI alpha 3′-UTR RNA sequences suggests that in HeLa cells, the longer 3′-UTR transcripts are likely to degrade approximately 13 times faster than the shorter 3′-UTR transcripts. This is the first report of a kinase mRNA containing multiple RNA-destabilising AREs in the longer of two mRNA transcripts.