Human CKIalpha(L) and CKIalpha(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-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 CKIalpha(L) and CKIalpha(S). We find human CKIalpha(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 CKIalpha(S). Both human CKIalpha(L), and CKIalpha(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.
Yong
T J
TJ
Division of Biology, National Institute of Education, Nanyang Technological University, Singapore.
Gan
Y Y
YY
Toh
B H
BH
Sentry
J W
JW
D020413:3' Untranslated Regions / Q000737:chemistry; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D047388:Casein Kinases; D018076:DNA, Complementary / Q000032:analysis / Q000302:isolation & purification; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009690:Nucleic Acid Conformation; D011494:Protein Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013379:Substrate Specificity
D020413:3' Untranslated Regions; D018076:DNA, Complementary; D012333:RNA, Messenger; D011494:Protein Kinases; D047388:Casein Kinases