Alternative processing of the tryptophanyl-tRNA synthetase mRNA from interferon-treated human cells.

We have analysed the structure of mRNA isoforms of the human gene encoding tryptophanyl-tRNA synthetase (Trp-tRNA synthetase) expressed in the epithelial CaOv cells and MT-4 lymphocytes. The Trp-tRNA synthetase gene is induced by interferon-gamma in both lines and, in MT-4 lymphocytes, also by interferon-alpha. Four Trp-tRNA synthetase mRNA isoforms have different combinations of the first exons IA, IB and II. Two transcription initiation sites (P1 and P2) were detected 90 bp from each other. Processing of the primary transcript initiated from the P1 start site generates the mRNA isoform where exon IA joins to exon II. The other three isoforms are produced by alternative splicing of the primary transcript produced from the P2 start site. Isoform 2 has a 3'-end fragment of exon IA joined to exon II. Isoform 3 contains exons IA and IB. Isoform 4 contains exon IA and exon III and lacks exon II encoding the N-terminus of the Trp-tRNA synthetase. Therefore, the two primary transcripts of the Trp-tRNA synthetase gene differ only in the 5' flank sequence between P1 and P2, and this fragment regulates their processing. Both interferon-alpha and interferon-gamma induce exon IA-containing and exon IB-containing isoforms of the Trp-tRNA synthetase mRNA.