Effect ofTPOgene mutations on the translational inhibition by upstream open reading frame (uORF) in the 5′-untranslated region of the TPO mRNA. The TPO coding region is shown as a thick blue arrow. A) Translation of normal TPO mRNA is physiologically almost completely inhibited by the presence of uORF7 in the 5′-UTR, which extends beyond the physiological start site. B) Mutations found in patients with hereditary thrombocytosis eliminate uORF7 in the 5′-untranslated region of the TPO mRNA and thereby allow the ribosome to efficiently initiate translation from the physiological translational start site (AUG).