The common 5' terminal sequence on trypanosome mRNAs: a target for anti-messenger oligodeoxynucleotides

Several mature mRNAs of Trypanosoma brucei were previously shown to have a common 5' terminal sequence of 35 nucleotides (nt) encoded by a separate mini-exon. To verify whether all trypanosome mRNAs contain this mini-exon sequence at their 5' end, we have tested oligodeoxynucleotides complementary to different parts of the 35 nt leader sequence for their ability to inhibit translation of total trypanosome mRNA. All oligomers tested inhibited translation of trypanosome mRNAs in a wheat germ extract. They had no effect on translation of Brome mosaic virus mRNA and of a trypanosome mRNA for phosphoglycerate kinase modified to remove the mini-exon sequence. Three different 12mers inhibited translation 35-60%; both the 22- and 34mer inhibited translation 95-100%. Incorporation of amino acids decreased proportionally in all protein bands detected in high resolution polyacrylamide gels. Our results show that all trypanosome mRNAs that yield a product detectable in gel contain a mini-exon sequence. We infer that most, if not all, trypanosome mRNAs contain a 5' terminal mini-exon sequence acquired by discontinuous synthesis.