(A) Structure of the human TPO gene. Exons are drawn as boxes and the protein coding region is shaded. Arrows mark the start sites for promoter 1 and 2 (P1 and P2). Solid lines connecting exons indicate normal splice events, dashed lines alternative splice events. ▵E2, exon 2 skipping. (B) Exon composition of the TPO mRNA splice variants. P1-wt and P2-wt, the full-length TPO mRNA transcribed from P1 or P2, respectively; P1▵E2, alternatively spliced TPO mRNA with exon 2 skipping. (C) Position of uAUG in the TPO 5′-UTR. The full-length mRNA sequence of the TPO 5′-UTR beginning with the P1 start site, as determined by Chang et al,32 is shown. Upstream AUG codons are boxed and numbered in the order as they appear. Translation of wild-type TPO protein starts at the eighth AUG (AUG 8). The deduced amino acid sequence is shown in the one-letter code. A stretch of GUG triplets is underlined. Triangles and Roman numerals mark the locations of introns.32 Filled arrowhead, P1 start site mapped by Chang et al32; gray arrowhead, P2 start site determined by Sohma et al37; open arrowheads, P2 start sites mapped by Kamura et al38 and Gurney et al.39