Activation of mts1 transcription by insertion of a retrovirus-like IAP element.

The mechanism of activation of mestatasis-associated mts1 gene transcription in the mouse myelomonocytic leukaemia WEHI-3 cell line is described. Northern blot analysis showed that WEHi-3 cells expressed two types of mts1-specific mRNA: standard (550 nt) and additional (about 800 nt). The steady-state expression level of the 800-nt RNA was isolated and sequence analysis showed that it contained a 357-bp fragment represented by long terminal repeat (LTR) sequences and a 5' untranslated region of the gag gene of the intracisternal A-particle (IAP) element. The chimeric IAP::mts1 800-nt mRNA is initiated from the 5' LTR promoter. The rearranged and normal loci of mts1 were cloned and partially sequenced. The results suggested that the insertion of the IAP sequences into the first intron of mts1 brings the gene under control of the strong IAP promoter. The additional chimeric 800-nt IAP::mts1 RNA transcript was the result of a splicing event linking IAP sequences with the coding part of mts1. We suggest that the chimeric IAP::mts1 RNA is capable of producing a functional Mts1 protein.