Overlapping reading frames are common in genomes of bacteriophages, bacteria and certain viruses. However, even in the latter cases, the overlaps are usually small, i.e. at most a few hundred nucleotides. In mammals, parts of two alternative proteins, p16INK4a and p19ARF, were shown to be generated from the same mouse INK4a tumor supressor gene, but each of the two proteins is still translated from its own mRNA.
In the July 16th issue of EMBO Journal, a German research team reveals a novel feature of the XL-exon of the rat Xlalphas/Galphas gene which encodes the N-terminal half of the neuroendocrine-specific G-protein alpha-subunit, XLalphas (Klemke et al., EMBO J 2001 Jul 16;20(14):3849-3860). This sequence bears an alternative open reading frame (ORF) that starts 32 nucleotides down-stream of the start codon for the XL-domain and encodes ALEX, a very basic protein of 356 amino acids. Both ALEX and XLalphas are translated from the same mRNA and, remarkably, ALEX binds to the XL-domain of XLalphas.
In addition, the authors pinpointed that the nucleotide sequence of the XL-exon shows a remarkably low level of conservation between species. Their findings, demonstrating a novel kind of genomic organization, allow them to conclude with an interesting model for co-evolution of ALEX and the XL-domain of XLalphas.
Wieland B. Huttner
Max-Planck-Institute of Molecular Cell Biology and Genetics
D – 01307 Dresden, Germany
Message posted by: Ulrike Sattler
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