Translational Repression of a Splice Variant of Cynomolgus Macaque CXCL1L by Its C-Terminal Sequence.

We previously isolated a cDNA clone from cynomolgus macaque encoding a novel CXC chemokine that we termed CXCL1L from its close similarity to CXCL1. However, the cDNA consisted of 3 exons instead of 4 exons that were typically seen in other CXC chemokines. Here, we isolated a cDNA encoding the full-length variant of CXCL1L that we termed CXCL1L beta. CXCL1L beta is 50 amino acids longer than the original CXCL1L, which we now term CXCL1L alpha. The CXCL1L beta mRNA is much more abundantly expressed in the cynomolgus macaque tissues than CXCL1L alpha mRNA. However, CXCL1L beta protein was poorly produced by transfected cells compared with that of CXCL1L alpha. When the coding region of the fourth exon was fused to the C-terminus of CXCL1 or even to a nonsecretory protein firefly luciferase, the fused proteins were also barely produced, although the mRNAs were abundantly expressed. The polysome profiling analysis suggested that the inhibition was mainly at the translational level. Furthermore, we demonstrated that the C-terminal 5 amino acids of CXCL1L beta were critical for the translational repression. The present study, thus, reveals a unique translational regulation controlling the production of a splicing variant of CXCL1L. Since the CXCL1L gene is functional only in the Old World monkeys, we also discuss possible reasons for the conservation of the active CXCL1L gene in these monkeys during the primate evolution.