Complex expression pattern of the TNF region gene LST1 through differential regulation, initiation, and alternative splicing

Recently, a novel gene, LST1, was identified in the tumor necrosis factor region of the HLA complex, 4 kb centromeric of the lymphotoxin beta gene. By analyzing several full-length cDNA clones and the genomic DNA, we identified seven exons and four introns, spanning 2.7 kb. Isolation of mouse LST1 cDNA clones established the open reading frame. LST1 transcription is characterized by four alternative transcription initiation sites and extensive alternative splicing. The derived polypeptides vary with regard to the presence of the hydrophobic N-terminus and in short internal sequences. In addition, alternative splicing results in LST1 mRNAs encoding different carboxy-terminal sequences. LST1 is predominantly transcribed in monocytes, and mRNA levels increase upon stimulation with interferon-gamma, with a concomitant change in the mRNA pattern resulting in an enhanced expression of the short LST1 transcripts. These data suggest that LST1 may have a specific role in monocytes and possibly also in T cells. Moreover, we found that the recently published cDNA 1C7 is encoded just centromeric of LST1. (C) 1997 Academic Press.