International E-publication: Publish Projects, Dissertation, Theses, Books, Souvenir, Conference Proceeding with ISBN.  International E-Bulletin: Information/News regarding: Academics and Research

Identification of a Chimeric Transcript formed by Intergenic Splicing of UbiE2 and Yghl1-4 in Mouse

    , , ,

Author Affiliations

  • 1Laboratory of Molecular Physiology, Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama 790-8566, Ehime, JAPAN

Int. Res. J. Biological Sci., Volume 3, Issue (3), Pages 52-59, March,10 (2014)

Abstract

We identified a chimeric transcript UbiE2-Yghl1-4, formed by an intergenic splicing event between UbiE2 and Yghl1-4 present in tandem position on the mouse chromosome 15F1 at a distance of ~3kb. The UbiE2 is S-adenosylmethionine-dependent methyltransferase domain containing protein encoding gene, also known as mettl7a2. The Yghl1-4 is a member of YGH1/HIG1 gene family in mouse with YGHL/HIG1 exon 3 domain. The chimeric transcript is formed with exon 1 of UbiE2 fused to exons 2-4 of Yghl1-4 using the canonical splice sites from both genes. The UbiE2-Yghl1-4 is not a product of in vitro artifacts and our results showed independent expression of the parent and the chimeric transcripts. The expression of UbiE2, Yghl1-4 and UbiE2-Yghl1-4 were found exclusive to kidney only. Further, tissue localization by Non-Radioactive In Situ Hybridization (NRISH) indicated restricted expression in the epithelium of proximal tubules and adrenal cortex. The UbiE2-Yghl1-4 gene formation was found only in mouse and not in human. The characteristics of the UbiE2-Yghl1-4 chimeric transcript being specific to mouse genome and containing both the methyl transferase domain and the YGHL/HIG1 exon 3 domain appears to have functional implications in mouse and especially in the kidney, rather than merely generating genetic diversity.

References

  1. Blencowe B. J., Alternative splicing: new insights from global analyses, Cell, 126(1), 37–47 (2006)
  2. Horiuchi T. and Aigaki T., Alternative trans-splicing: a novel mode of pre-mRNA processing, Biol. Cell., 98(2), 135–140 (2006)
  3. Pradet-Balade B., Medema J.P., Lσpez-Fraga M., Lozano J.C., Kolfschoten G.M., Picard A., et al., An endogenous hybrid mRNA encodes TWE-PRIL, a functional cell surface TWEAK-APRIL fusion protein, EMBO J., 21(21), 5711-5720 (2002)
  4. Akiva P., Toporik A., Edelheit S., Peretz Y., Diber A., Shemesh R., et al., Transcription-mediated gene fusion in the human genome, Genome Res., 16(1), 30–36 (2006)
  5. Roux M., Levιziel H., and Amarger V., Cotranscription and intergenic splicing of the PPARG and TSEN2 genes in cattle, BMC genomics 7(1), 71 (2006)
  6. Babushok D. V., Ostertag E. M. and Kazazian H. H., Current topics in genome evolution: molecular mechanisms of new gene formation, Cell. Mol. Life Sci., 64(5), 542–554 (2007)
  7. Frenkel-Morgenstern M., Gorohovski A., Lacroix V., Rogers M., Ibanez K., Boullosa C., et al., ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data, Nucleic Acids Res., 41, 142–151 (2012a)
  8. Frenkel-Morgenstern M., Lacroix V., Ezkurdia I., Levin Y., Gabashvili A., Prilusky J., et al., Chimeras taking shape: potential functions of proteins encoded by chimeric RNA transcripts, Genome Res., 22(7), 1231–1242 (2012b)
  9. Kim D.S., Kim D.W., Kim M.Y., Nam S.H., Choi S.H., Kim R.N., et al., CACG: a database for comparative analysis of conjoined genes, Genomics, 100(1), 14–17 (2012)
  10. Magrangeas F., Pitiot G., Dubois S., Bragado-Nilsson E., Chιrel M., Jobert S., et al., Cotranscription and intergenic splicing of human galactose-1-phosphate uridylyltransferase and interleukin-11 receptor alpha-chain genes generate a fusion mRNA in normal cells. Implication for the production of multidomain proteins during evolution, J. Biol. Chem., 273(26), 16005–16010 (1998)
  11. Finta C. and Zaphiropoulos P. G., The human CYP2C locus: a prototype for intergenic and exon repetition splicing events, Genomics, 63(3), 433–438 (2000)
  12. Thomson T.M., Lozano J.J., Loukili N., Carrio R., Serras F., Cormand B., et al., Fusion of the human gene for the polyubiquitination coeffector UEV1 with Kua, a newly identified gene, Genome Res., 10, 1743–1756 (2000)
  13. Communi D., Suarez-Huerta N., Dussossoy D., Savi P. and Boeynaems J. M., Cotranscription and intergenic splicing of human P2Y11 and SSF1 genes, J. Biol. Chem., 276(19), 16561–16566 (2001)
  14. Naganuma S., Itoh H., Uchiyama S., Tanaka H., Nagaike K., Miyata S., et al., Characterization of transcripts generated from mouse hepatocyte growth factor activator inhibitor type 2 (HAI-2) and HAI-2-related small peptide (H2RSP) genes: chimeric mRNA transcribed from both HAI-2 and H2RSP genes is detected in human but not in mouse, Biochem Biophys Res Commun.302(2), 345–353 (2003)
  15. Poulin F., Brueschke A., and Sonenberg N., Gene fusion and overlapping reading frames in the mammalian genes for 4E-BP3 and MASK, J. Biol. Chem., 278(52), 52290–52297 (2003)
  16. Maeda K., Horikoshi T., Nakashima E., Miyamoto Y., Mabuchi A., and Ikegawa S., MATN and LAPTM are parts of larger transcription units produced by intergenic splicing: intergenic splicing may be a common phenomenon, DNA Res., 12(5), 365–372 (2005)
  17. Parra G., Reymond A., Dabbouseh N., Dermitzakis E. T., Castelo R., Thomson T. M., et al., Tandem chimerism as a means to increase protein complexity in the human genome, Genome Res., 16(1), 37–44 (2006)
  18. Dalziel M., Kolesnichenko M., Das Neves R. P., Iborra F., Goding C. and Furger A. Alpha-MSH regulates intergenic splicing of MC1R and TUBB3 in human melanocytes, Nucleic Acids Res., 39(6), 2378–2692 (2011)
  19. Abe S., Ravi N.S., Sahi V.P. and Morita E.H., Identification and characterization of the YGHL1 gene from Yellowtail fish (Seriola quinqueradiata) and the evolution of the YGHL1/HIG1 family in vertebrates, Int. Res. J. Biological Sci., 2(9), 59-68 (2013)
  20. Gracey A.Y., Troll J.V. and Somero G.N., Hypoxia-induced gene expression profiling in the euryoxic fish Gillichthys mirabilis, Proc. Natl. Acad. Sci. U.S.A., 98, 1993-1998 (2001)
  21. Klein S.L., Strausberg R.L., Wagner L., Pontius J., Clifton S.W. and Richardson P., Genetic and genomic tools for Xenopus research: The NIH Xenopus initiative, Dev. Dyn., 225 (4), 384-391 (2002)
  22. Chen S.L., Xu M.Y., Hu S.L. and Li L., Analysis of immune-relevant genes expressed in red sea bream spleen, Aquaculture,240, 115-130 (2004)
  23. Caldwell R.B., Kierzek A.M., Arakawa H., Bezzubov Y., Zaim J., Fiedler P., et al., Full-length cDNAs from chicken bursal lymphocytes to facilitate gene function analysis, Genome Biol, 6 (1), R6 (2005)
  24. Kim Y.O., Park E.M., Moon J.Y., Kong H.J., Nam B.H., Kim W.J., et al., Molecular characterization and transcriptional analysis of the olive flounder (Paralichthys olivaceus) YGHL1 gene in response to hypoxia and infection, Mol. Cell. Biochem.,357 (1-2), 305-312 (2011)
  25. Kessel M. and Gruss P., Murine developmental control genes, Science,249, 374-379 (1990)
  26. Nadeau J.H. and Sankoff D., Comparable rates of gene loss and functional divergence after genome duplications early in vertebrate evolution, Genetics, 147, 1259–1266 (1997)
  27. Gibson T.J. and Spring J., Genetic redundancy in vertebrates: polyploidy and persistence of genes encoding multidomain proteins, Trends Genet., 14, 46-49 (1998)
  28. Otto S.P., The evolutionary consequences of polyploidy, Cell, 131(3), 452-462 (2007)
  29. Gerstein A.C. and Otto S.P., Ploidy and the causes of genomic evolution, J. Hered., 100(5), 571-581 2009)30.Zaphiropoulos P.G., Template switching generated during reverse transcription?, FEBS Lett., 527(1-3), 326 (2002)
  30. Mayer M.G. and Floeter-Winter L.M., Pre-mRNA transsplicing: from kinetoplastids to mammals, an easy language for life diversity, Mem Inst Oswaldo Cruz.100, 501-513 (2005)
  31. Gingeras T.R., Implications of chimaeric non-co-linear transcripts, Nature, 461, 206–211 (2009)
  32. Li X., Zhao L., Jiang H., and Wang W., Short homologous sequences are strongly associated with the generation of chimeric RNAs in eukaryotes, J. Mol. Evol., 68(1), 56–65 (2009)
  33. Zaphiropoulos P. G., RNA molecules containing exons originating from different members of the cytochrome P450 2C gene subfamily (CYP2C) in human epidermis and liver, Nucleic Acids Res., 27(13), 2585–2590 (1999)
  34. Finta C. and Zaphiropoulos P.G., Intergenic mRNA molecules resulting from trans-splicing, J. Biol. Chem., 277, 5882–5890 (2002)
  35. Tasic B., Nabholz C.E., Baldwin K.K., Kim Y., Rueckert E.H., Ribich S.A., et al., Promoter choice determines splice site selection in protocadherin a and g pre-mRNA splicing, Mol. Cell., 10, 21-33 (2002)
  36. Millar J.K., Christie S., Semple C.A. and Porteous D.J., Chromosomal Location and Genomic Structure of the Human Translin-Associated Factor X Gene (TRAX; TSNAX) Revealed by Intergenic Splicing to DISC1, a Gene Disrupted by a Translocation Segregating with Schizophrenia, Genomics, 67(1), 69-77 (2000)
  37. Prakash T., Sharma V.K., Adati N., Ozawa R., Kumar N., Nishida Y., et al., Expression of conjoined genes: another mechanism for gene regulation in eukaryotes, PLoS One, 5(10), e13284 (2010)