ACTIVATION OF MTS1 TRANSCRIPTION BY INSERTION OF A RETROVIRUS-LIKE IAP ELEMENT

The mechanism of activation of metastasis-associated mts1 gene transcr iption in the mouse myelomonocytic leukaemia WEHI-3 cell line is descr ibed. Northern blot analysis showed that WEHI-3 cells expressed two ty pes of mts1-specific mRNA: standard (550 nt) and additional (about 800 nt). The steady-state expression level of the 800-nt mRNA was 10-fold higher than that of the 550-nt mRNA. A cDNA clone corresponding to th e 800-nt RNA was isolated and sequence analysis showed that it contain ed a 357-bp fragment represented by long terminal repeat (LTR) sequenc es and a 5' untranslated region of the gag gene of the intracisternal A-particle (IAP) element. The chimeric IAP::mts1 800-nt mRNA is initia ted from the 5' LTR promoter. The rearranged and normal loci of mts1 w ere cloned and partially sequenced. The results suggest that the inser tion of the IAP sequences into the first intron of mts1 brings the gen e under control of the strong IAP promoter. The additional chimeric 80 0-nt IAP::mts1 RNA transcript was the result of a splicing event linki ng IAP sequences with the coding part of mts1. We suggest that the chi meric IAP::mts1 RNA is capable of producing a functional Mts1 protein.