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

Casein kinase I (CKI) are a family of conserved second messenger-independen t serine/threonine protein kinases found in all eukaryotes. The avian and m ammalian CKI alpha isoform has four splice variants differing in the presen ce or absence of 28 amino acids ('(L)' insertion) in the catalytic domain a nd/or 12 amino acids ('(S)' insertion) in the regulatory domain. Here we re port the isolation of cDNAs encoding human CKI alpha(L) and CKI alpha(S). W e find human CKI alpha(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 CKI alpha(S). Both human CKI alpha(L), and CKI alpha(S) are derived from 4.2-kb mRNA transcripts and 2.4-kb transcripts, the latter pro bably generated by use of an alternate polyadenylation signal identified in the longer transcripts. The 4.2-kb transcripts contain six RNA-destabilisi ng 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 sh orter 3'-UTR transcripts. This is the first report of a kinase mRNA contain ing multiple RNA-destabilising AREs in the longer of two mRNA transcripts. (C) 2000 Elsevier Science B.V. All rights reserved.