Genomics & Informatics

Korea Genome Organization (한국유전체학회)
권호 표지

High Correlation between Alu Elements and the Conversion of 3' UTR of mRNAs Processed Pseudogenes

  • An, Hyeong Jun (Department of BioSystems, Korea Advanced Institute of Science and Technology) ;
  • Na, Dokyun (Department of BioSystems, Korea Advanced Institute of Science and Technology) ;
  • Lee, Doheon (Department of BioSystems, Korea Advanced Institute of Science and Technology) ;
  • Lee, Kwang Hyung (Department of BioSystems, Korea Advanced Institute of Science and Technology) ;
  • Bhak, Jonghwa (Department of BioSystems, Korea Advanced Institute of Science and Technology)
  • Published : 2004.06.01
Download PDF
⟨ Previous Next ⟩

Abstract

Even though it represents $6-13\%$ of human genomic DNA, Alu sequences are rarely found in coding regions. When in exon region, over $80\%$ of them are found in 3' untranslated region (UTR). Pseudogenes are an important component of human genome. Their functions are not clearly known and the mechanism of how they are generated is still debatable. Both the Alu and Pseudogenes are important research problems in molecular biology. mRNA is thought to be a prime source of pseudogene and active research is going on its molecular mechanism. We report, for the first time, that mRNAs containing Alu repeats at 3' UTR has a significantly high correlation with processed pseudogenes, suggesting a possibility that Alu containing mRNAs have a high tendency to become processed pseudogenes. It is known that about $10\%$ of all human genes have been transposed. Transposed genes at 3' UTR without Alu repeat have about two processed pseudogenes per gene on average while we found with statistical significance that a transposed gene with Alu had over three processed Pseudogenes on average. Therefore, we propose Alu repeats as a new and important factor in the generation of pseudogenes.

Keywords

References

  1. Altschul, S.F., Gish, W., Miller, W., Myers, E.W., and Lipman, D.J. (1990). Basic local alignment search tool. J. Mol. Biol. 215:403-410
  2. Altschul, S.F., Madden, T.L., Sch$\"a$ffer, A.A., Zhang, J., Zhang, Z., Miller, W., and Lipman, D.J. (1997). Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25:3389-3402 https://doi.org/10.1093/nar/25.17.3389
  3. Boeke, J.D. (1997). LINE and Alus -the poIyA connection. Nature Genet. 16, 6-7 https://doi.org/10.1038/ng0597-6
  4. Deininger, P. L. and Batzer, M. A. (1999). Alu repeats and Human Disease. Melecular Genetics and Metabolism 67, 183-193 https://doi.org/10.1006/mgme.1999.2864
  5. Dewannieux, M., Esnault, C., and Heidmann, T. (2003). LINE-mediated retrotransposition of marked Alusequences. Nature Genetics 35, 41-48 https://doi.org/10.1038/ng1223
  6. Esnault, C., Maestre, J., and Heidmann, T. (2000). Human LINE retrotranspsposons generate processed pseudogenes. Nature Genet 24, 363-367 https://doi.org/10.1038/74184
  7. Gish, W. and States, D.J. (1993). Identification of protein coding regions by database similarity search. Nature Genet. 3:266-272 https://doi.org/10.1038/ng0393-266
  8. Harrison, P. M., Hegyi, H., Balasubramanian, S., Luscombe, N. M., Bertone P., Echols, N., Johnson, T., and Gerstein, M. (2002). Molecular fossils in the Human Genome: identification and Analysis of the pseudogenes in chromosomes 21 and 22, Genome Res. 12, 272-280 https://doi.org/10.1101/gr.207102
  9. Kazazian, H.H. Jr. (2004). Mobile elements: drivers of genome evolution. Science 303, 1626-1632 https://doi.org/10.1126/science.1089670
  10. Kazazian, H.H. Jr. and Goodier J.L. (2002). LINE drive. retrotransposition and genome instability. Cell 110, 277-280 https://doi.org/10.1016/S0092-8674(02)00868-1
  11. Kurose K., Hata K., Hattori, M., and Sakaki, Y. (1995). RNA polymerase III dependence of the human L1 promoter and possible participation of the RNA polymerase II factor YY1 in the RNA polymerase II factor YY1 in the RNA polymerase III transcription system. Nucleic Acids Res. 23, 3704-3709 https://doi.org/10.1093/nar/23.18.3704
  12. Lander, E.S., Linton, L.M., Birren, B., Nusbaum, C., and Zody, M.C., (2001). Initial sequencing and analysis of the human genome. Nature 409, 860-921 https://doi.org/10.1038/35057062
  13. Madden, T.L., Tatusov, R.L., and Zhang, J. (1996). Applications of network BLAST server. Meth. Enzymol. 266:131-141 https://doi.org/10.1016/S0076-6879(96)66011-X
  14. Maestre, J., Tchenio, T., Dhellin O., and Heidmann T. (1995). mRNAs retroposition in human cells: processed pseudogene formation. EMBO J. 14, 6333-6338
  15. Mighell, A.J., Markham, A.F., and Bobinson, P.A. (1997). Alu sequences. FEBS Lett. 417, 1-5 https://doi.org/10.1016/S0014-5793(97)01259-3
  16. Mighell, A.J., Smith, N.R., Robinson, P.A., and Markham, A.F. (2000). Vertebrate pseudogenes. FEBS Lett. 468, 109-114 https://doi.org/10.1016/S0014-5793(00)01199-6
  17. Moran, V., DeBerardinis, J., and Kazazian, H.H. Jr. (1999). Exon Shuffling by L1 Retrotransposition. Science 283, 1530-1543 https://doi.org/10.1126/science.283.5407.1530
  18. Ostertag, M. and Kazazian, H.H. Jr. (2001). Biology of mammalian L1 retrotransposons. Annu. Rev. Genet. 35, 501-538 https://doi.org/10.1146/annurev.genet.35.102401.091032
  19. Rebhan, M., Chalifa-Caspi, V., Prilusky, J., and Lancet, D. (1997). GeneCards: integrating information about genes, proteins and diseases. Trends in Genetics 13, 163 https://doi.org/10.1016/S0168-9525(97)01103-7
  20. Wei, W., Gilbert, N., Ooi, S.L, Lawler, J.F., Ostertag, E.M., Kazazian, H.H. Jr., Boeke, J.D., and Moran, J.V. (2001). Human L1 retrotransposition: cis preference versus trans complementation. Mol. Cell. Biol. 21, 1429-1439 https://doi.org/10.1128/MCB.21.4.1429-1439.2001
  21. Weiner, A. M., Deininger, P. L., and Efstratiadis, A.. (1986). Nonviral retroposons: Genes, Pseudogenes and transposable elements generated by the reverse flow of genetic information. Annu. Rev. Biochem. 55, 631-662 https://doi.org/10.1146/annurev.bi.55.070186.003215
  22. Yulung, G., Yulung, A. and Fisher, E.M.C. (1995). The frequency and position of Alu repeats in cDNAs, as determined by database searching. Genomics 27, 544-548 https://doi.org/10.1006/geno.1995.1090
  23. Zhang, J. and Madden, T.L. (1997). PowerBLAST: A new network BLAST application for interactive or automated sequence analysis and annotation. Genome Res. 7:649-656 https://doi.org/10.1101/gr.7.6.649
  24. Zhang, Z., Harrison, P. M., Liu, Y., and Gerstein, M. (2003). Millions of years of evolution preserved: A comprehensive catalog of the processed pseudogenes in the human genome. Genome Res. 13, 2541-2558 https://doi.org/10.1101/gr.1429003