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

A number of growth factors, whose spatio-temporal expression is essential f or 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 ( IGFI1) with one upstream open reading frame and stable stem-loop structures , elements which might be important for controlled translation. To investig ate whether these unusual features of IGFI1 can control translation initiat ion during embryogenesis, we examined the initiation efficiency on this 5'U TR during development of Xenopus laevis. The results demonstrate that IGFI1 strongly represses translation of a reporter in early embryos, compared wi th the Xenopus beta -globin 5'UTR. The inhibition is alleviated soon after the midblastula transition, suggesting a stimulatory effect of the transcri ption start. However, a similar stimulation of IGFI1-driven translation is seen in embryos in which de novo transcription was inhibited by actinomycin D. Furthermore, it is shown that up-regulation of IGFI1 activity is indepe ndent of elF4E levels, and activity of IGFI1 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 co mplex 5'UTR after the midblastula transition.