Dual‐coding Regions in Alternatively Spliced Human Genes

By using different exon combinations, alternatively spliced genes may contain dual-coding regions, where more than one reading frame encodes amino acid sequences. These special coding regions generate functionally related but distinct protein products and evolve under unusual selective forces.

Keywords: alternative splicing; reading frame; in-frame stop; overlapping genes

Figure 1. Three known examples of dual-coding genes in mammals. (a) A transcript of the Gnas1 gene contains two reading frames and produces two structurally unrelated proteins, XLs and ALEX, using different translation start sites. (b) A newly transcribed XBP1 mRNA can only produce protein XBP1U from ORF A. Removal of a 26-bp spacer (dark gray rectangle) joins the beginning of ORF A with ORF B and translation produces a different product, XBP1S. (c) Ink4a generates two splice variants that use different reading frames within exon E2 to produce the proteins p16Ink4a and p19ARF. Reproduced with permission from Chung et al. (2007).
Figure 2. Schematic representation of a dual-coding region in the human ITGB4BP gene. Exons are represented by boxes and introns by connecting lines. Numbers inside the boxes refer to base pairs. Roman numerals indicate intron phases. The dual-coding region is marked by a black horizontal arrow. Orthologous sequences for this region are shown in other species, and in-frame stop codons are marked by an underlined X. Bioinformatic supporting evidence for the use of both reading frames in humans is shown in the table on the left. The table on the right summarizes the presence of stop codons in orthologous sequences in two reading frames. White arrows indicate direction of data flow for bioinformatics analysis. NM_181466 and NM_181467 are RefSeq accession numbers. Reproduced from Liang and Landweber (2006) by permission of Cold Spring Harbor Laboratory Press.
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Liang, Han, and Landweber, Laura F(Mar 2008) Dual‐coding Regions in Alternatively Spliced Human Genes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020780]