THE RU5 (R) REGION FROM HUMAN LEUKEMIA VIRUSES (HTLV-1) CONTAINS AN INTERNAL RIBOSOME ENTRY SITE (IRES)-LIKE SEQUENCE

RNA fragments containing the complete R region and the beginning of th e U5 region ('R') from the human T cell leukaemia virus 1 (HTLV-1) sti mulated the translation of the second cistrons in bicistronic mRNAs, T he 5' untranslated region from SV40 early genes (SU) which was unable to stimulate translation of second cistrons amplified markedly the int ernal ribosome entry site (TRES) effect of the HTLV-1 'R' fragments. T be 'R' regions from HTLV-1 have therefore properties similar to intern al ribosome entry sites (IRES) originally found in picornavirus. The b eginning of the U5 region from HTLV-1 contains a polypyrimidine sequen ce which is known to play an essential role in the IRES activity in pi cornavirus. The same experiments carried out using the 'R' region from bovine leukaemia virus (BLV) showed that this sequence has at most a weak IRES effect, One retroviruses HTLV-1 and perhaps others contain t herefore an IRES activity, Interestingly, the combined SU 'R' sequence worked efficiently with different cistrons, different promoters and i n all tested cell lines, whereas the poliovirus IRES was active in CHO cells but not in the mouse mammary cell line HC11, The SU 'R' sequenc e may therefore preferably be used to generate active bicistronic mRNA s.