The 5' untranslated region, signal peptide, and the coding sequence of the carboxyl terminus of IL-15 participate in its multifaceted translational control.
We previously reported that the AUG-burdened 5' untranslated region (UTR) of IL-15 mRNA impedes its translation. Here we demonstrate that the nucleotide or protein sequences of the IL-15 signal peptide and carboxyl terminus also contribute to the poor translation of IL-15 transcripts. In particular, the exchange of the IL-15 signal peptide coding sequence with that of IL-2 increased cellular and secreted levels of IL-15 protein 15- to 20-fold in COS cells, while IL-2 transcripts with the IL-15 signal peptide generated 30- to 50-fold less IL-2 protein than wild-type IL-2. Furthermore, the addition of an artificial epitope tag to the 3' coding sequence of IL-15 increased its protein production 5- to 10-fold. Combining these two IL-15 message modifications, in addition to removing the 5' UTR, increased IL-15 synthesis 250-fold compared with a wild-type construct with an intact 5' UTR. These data suggest that IL-15 mRNA, unlike IL-2 mRNA, may exist in translationally inactive pools. By storing translationally quiescent IL-15 mRNA, cells might respond to intracellular infections or other stimuli by rapidly transforming IL-15 message into one that can be efficiently translated.
Bamford
R N
RN
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
DeFilippis
A P
AP
Azimi
N
N
Kurys
G
G
Waldmann
T A
TA
D000818:Animals; D019556:COS Cells; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000235:genetics*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017421:Sequence Analysis; D014162:Transfection
D019409:Interleukin-15; D012333:RNA, Messenger