Controlled translation initiation on insulin-like growth factor 2-leader 1 during Xenopus laevis embryogenesis

A number of growth factors, whose spatio-temporal expression is essential for embryonic development, are encoded by mRNAs with a complex 5'UTR. Human insulin-like growth factor 2 mRNA contains a long (592 nucleotides) 5'UTR (IGFl1) with one upstream open reading frame and stable stem-loop structures, elements which might be important for controlled translation. To investigate whether these unusual features of IGFl1 can control translation initiation during embryogenesis, we examined the initiation efficiency on this 5'UTR during development of Xenopus laevis. The results demonstrate that IGFl1 strongly represses translation of a reporter in early embryos, compared with the Xenopus beta-globin 5'UTR. The inhibition is alleviated soon after the midblastula transition, suggesting a stimulatory effect of the transcription start. However, a similar stimulation of IGFl1-driven translation is seen in embryos in which de novo transcription was inhibited by actinomycin D. Furthermore, it is shown that up-regulation of IGFl1 activity is independent of eIF4E levels, and activity of IGFl1 is observed in all tissues of transgenic Xenopus embryos. These results indicate that post-translational modulation of a trans-acting factor enables efficient initiation on this complex 5'UTR after the midblastula transition.