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hRap1B-retro: a novel human processed Rap1B gene blurs the picture?

Leukemia volume 20, pages 145–146 (2006)Cite this article

In the September issue of Leukemia, Gyan et al.1 report on the expression of a mutant Rap1B cDNA in myelodysplastic syndromes (MDS). Specifically, they detect a cDNA with point mutations, as compared to the wild-type Rap1B gene, that cause two amino-acid substitutions (G12R and K42E). Unfortunately, the authors could not perform an analysis of genomic DNA, which would directly reveal the relation between the Rap1B gene and the mutant cDNA. Although they point out correctly that the encoded protein most likely constitutes an activated form of Rap1B protein, we hereby present strong evidence that the detected cDNA does not originate from mutation of the Rap1B gene on chromosome 12.

Direct evidence for expression of hRap1B-retro comes from analysis of full-length expressed cDNAs deposited in the NCBI database. Interestingly, three of the cDNAs were cloned from a Ramos Burkitt's lymphoma cell line (GIs: 50475494, 50474682, 50470789), one was isolated from a neuroblastoma cell line (GI: 50498405), and one from a placental library (GI: 50492447). These sequences map exactly onto the genomic DNA sequence on chromosome 5 (Figure 1, Supplementary Figure 1), revealing a structure of the hRap1B-retro gene with two exons (Figure 1, Supplementary Figure 2). As genomic sequences of processed genes are expected to lack intronic sequences, we set out to analyse this observed peculiarity closely. We found that the intron was created via LINE-1-mediated insertion of the SVA element into a preferred target site sequence (TTTT/AA)4 present in hRap1B mRNA at 1304 (GI: 58219793). Since this intronic region is missing from the sequences of the five deposited in database cDNAs, it is evident that they represent transcribed and spliced sequences rather than contaminating genomic DNA.

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References

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Acknowledgements

TZ thanks Professor Martin Vingron for the helpful discussions and support. TZ acknowledges support received from the BioSapiens Network of Excellence, funded by the European Commission within its FP6 Programme, under the thematic area ‘Life sciences, genomics and biotechnology for health’, contract number LHSG-CT-2003-503265.

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Authors and Affiliations

  1. Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany

    T Zemojtel

  2. In Silico Miners, Berlin, Germany

    T Zemojtel, T Penzkofer & M Duchniewicz

  3. Biozentrum, Am Hubland, Wuerzburg, Germany

    T Penzkofer

  4. Department of Physiological Chemistry and the Centre for Biomedical Genetics, University Medical Centre Utrecht, CG Utrecht, The Netherlands

    F J T Zwartkruis

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  1. T Zemojtel
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  2. T Penzkofer
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  4. F J T Zwartkruis
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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu).

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Zemojtel, T., Penzkofer, T., Duchniewicz, M. et al. hRap1B-retro: a novel human processed Rap1B gene blurs the picture?. Leukemia 20, 145–146 (2006). https://doi.org/10.1038/sj.leu.2404040

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