Figure 7. Model of the alternative use of upstream open reading frames in the Shank1 mRNA.

A. In the Shank1 5′UTR, the scanning 40S subunit of the ribosome encounters strong secondary structure, blocking access to translation start sites. These difficulties may be overcome either with the help of associated RNA helicase activities (h arrow) or by a shunting mechanism (s arrow). After reaching uAUG3, uORF3 (red) is translated and reinitiation at AUG⁺²¹⁴ leads to synthesis of the short form of the mature Shank1 protein (blue). B. Alternatively, the non-canonical ACG start codon is used; uORF0 (red) is translated, allowing the 80S ribosome to proceed beyond uAUG3. Reinitiation occurs at AUG⁺¹, leading to synthesis of the long version of Shank1 (blue).