Figure 9.

A model for the regulation of Zeb2 expression in epithelial and mesenchymal cells. (Left side, 1) In epithelial cells transcription of the main promoter of Zeb2 gene (in black) generates an RNA composed of a 3-kb 5′-UTR (in gray) and the ORF (in white). Upon binding of the spliceosome (2), an intron corresponding to 2.5 kb is eliminated, generating a processed transcript with a 5′-UTR of 481 nt (3). (4) This 5′-UTR contains a sequence that inhibits scanning by the ribosomes and therefore prevents translation of Zeb2 protein. (Right side, 5) After completion of the EMT, transcription of Zeb2 is accompanied by expression of a NAT depending on the activation of a different promoter placed 5′ downstream. Expression of this NAT is greater than the long transcript (not shown) and prevents binding of the spliceosome to the 5′ splice site (6) and, consequently, the intron present in the 5′-UTR is conserved (7). This intron contains an IRES situated close to the start of translation. Binding of the ribosomes to this IRES (8) makes the translation of Zeb2 protein possible (9).