THE HUMAN INSULIN-LIKE GROWTH-FACTOR-II LEADER-1 CONTAINS AN INTERNALRIBOSOMAL ENTRY SITE

Insulin-like growth factor II is a small peptide growth hormone, encod ed by four mRNAs with unique 5' untranslated regions and identical cod ing regions. The 5' untranslated region transcribed from promoter 1 is 598 nt (leader 1). The properties of this leader 1 suggest a strong r egulation of translation; the high G + C-content, the presence of an u pstream open reading frame, and the length of the 5' UTR are 3 element s which prohibit efficient translation and which may modulate expressi on. In this paper we show that the human IGFII leader 1 harbours seque nce elements that allow translation initiation to occur by internal in itiation on the IGF sequence. This mode of initiation was described fi rst for picornaviral mRNAs, that are naturally uncapped. The IGFII lea der I-dependent expression in HeLa cells was resistant to infection wi th poliovirus; abrogation of cap-dependent initiation by poliovirus ha d apparently no effect on IGFII expression. Moreover, a downstream CAT -cistron in a bicistronic construct was translated upon insertion of t he leader 1 sequence. The translational properties of the IGFII leader 1 suggest that internal initiation on this leader may be modulated du ring proliferation or differentiation, enabling cell-stage dependent e xpression of IGFII.