Identification of an alternatively spliced transcript of human interleukin-4 lacking the sequence encoded by exon 2.

The expression of interleukin-4 (IL-4) mRNA of human peripheral blood mononuclear cells stimulated with phytohemagglutinin (PHA) for 15 hours was analyzed by reverse transcription and subsequent polymerase chain reaction (RT/PCR). These analyses revealed an additional smaller fragment that hybridizes with an IL-4 cDNA probe and an oligonucleotide that is specific for a fragment lacking the sequence encoded by exon 2. Sequencing of this fragment demonstrates that it is generated from an alternatively spliced transcript of the IL-4 gene with the sequence encoded by exon 2 being skipped. Skipping of exon 2 does not result in a frame shift but would delete part of the mature protein (48 bp coding for amino acid residues 22 to 37), including Cys24 but not a region directly involved in receptor binding. Differential splicing of other exons or exon combinations has not been observed. The data suggest that the alternatively spliced transcript is not generated by a splicing or PCR error and is not detectable solely because of the high sensitivity of RT/PCR, but in contrast, argue for a physiological role of the transcript and its potentially encoded protein.