Alternative splicing of the Evi-1 zinc finger gene generates mRNAs which differ by the number of zinc finger motifs

Abstract

Evi-1 is a common integration site for endogenous ecotropic virus in myeloid leukemias of the AKXD mouse strain. This gene encodes a zinc finger protein with ten finger motifs. Myeloblastic leukemias obtained after infection with F-MuLV frequently exhibit proviral integration in the Fim-3 region which is genetically linked to Evi-1. This proviral integration always results in the expression of two mRNA transcripts, 5.7 kb and 4.7 kb long. We isolated two classes of cDNAs from a myeloblastic cell line with a F-MuLV provirus integrated in Fim-3. By sequence analysis, we found that one Evi-1 cDNA (E29) had an internal deletion of 972 nucleotides when compared to the full-length sequence previously published by Morishita et al. (1988). This deletion eliminated the 6th and 7th Evi-1 finger domains and was bordered by consensus donor and acceptor splice sequences. The E29 clone most likely resulted from alternative splicing of the Evi-1 gene. This was confirmed by Northern blot analysis and S1 mapping experiments. Therefore, the Evi-1 gene codes potentially for at least two proteins of 1042 and 718 amino acids differing in the numbers of their zinc-finger motifs.