Alternative splicing of mouse IL-15 is due to the use of an internal splice site in exon 5

IL-15 is a pleiotropic cytokine modulating growth and differentiation of se veral hematopoietic cell types. Recently, we have demonstrated that mouse m icroglial cells, the brain macrophages, express both IL-15 and IL-15/IL-2 r eceptors. Based on single-cell RT-PCR data, we describe here an alternative ly spliced IL-15 mRNA variant found in a small subpopulation of mouse micro glia (5%, 3 out of 60 cells expressing IL-15 transcripts). PCR cycle sequen cing of this larger transcript revealed the mouse homologue of the alternat ively spliced exon A as it is known from the human IL-15 gene. Analysis of the corresponding mouse IL-15 gene region shows that the larger IL-15 trans cript contains an yet unidentified 5' sequence of exon 5 while the shorter transcript uses an internal splice acceptor site. The mouse exon 5A segment has a length of 136 nt (17 nt longer than the human exon A). It contains f ive in-frame stop codons at its 5' end and a new translation initiation sit e at its 3' end. This new start site is surrounded by a favourable Kozak co nsensus sequence suggesting a more efficient translation rate. Further tran slational control by stem-loop binding factors is inferred by a predicted R NA stem-loop structure around the start site. Insertion of exon 5A would le ad to an IL-15 polypeptide with a shortened leader sequence of 26 amino aci ds, as compared to the 48 amino acid leader sequence encoded by the transcr ipt lacking exon 5A. Thus, the final IL-15 protein of the two splice varian ts is identical; different leader sequences could, however, lead to differe nces in the intracellular sorting, processing and/or secretion of IL-15. (C ) 1998 Elsevier Science B.V. All rights reserved.