ИСТИНА

Despite many efforts, mechanism of HIV-1 mRNAs translation still remains obscure. Conventional wisdom says that it can use both scanning mechanism and internal initiation, the latter prevailing in G2/M-phase. However, since existing reports are equivocal, we performed extensive analysis of the unspliced HIV-1 mRNA 5′UTR using stringent criteria for an IRES identification, that have been recently developed in our lab. Our results strongly point to the lack of any IRES in HIV-1 mRNA leader. First, direct comparison of translation efficiencies of monocistronic versus bicistronic mRNAs revealed that HIV-1 mRNA 5′UTR promotes internal initiation rather poorly both in vitro and in vivo. In addition, monocistronic mRNA translation was strongly stimulated by capping and, moreover, translation of both capped and uncapped mRNAs was severely inhibited by introduction of upstream AUG-codons to a similar extent. These results were reproduced in several unsynchronized cell lines, including Jurkat cells, as well as in G2/M-stalled ones. Overall, we conclude that HIV-1 mRNA is translated exclusively in a cap-dependent fashion.