title: The 5' untranslated region, signal peptide, and the coding sequence of the carboxyl terminus of IL-15 participate in its multifaceted translational control.
abstract: 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.
authors.affiliation: Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Bamford
authors.forename: A P
authors.initials: AP
authors.lastname: DeFilippis
authors.forename: N
authors.initials: N
authors.lastname: Azimi
authors.forename: G
authors.initials: G
authors.lastname: Kurys
authors.forename: T A
authors.initials: TA
authors.lastname: Waldmann
mesh_terms: 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
chemical_list: D019409:Interleukin-15; D012333:RNA, Messenger