Abstract
There is a growing evidence, that antisense transcription might have a key role in a range of human diseases. Although predefined sense-antisense pairs were extensively studied, the antisense expression of the known sense genes is rarely investigated. We retrieved and correlated the expression of sense and antisense sequences of 1182 mouse transcripts to assess the prevalence and to find the characteristic pattern of antisense transcription. We contrasted three Affymetrix MGU74A version 1 mouse genome chips to six MGU74A version 2 chips. For these 1182 transcripts, the version 1 chips contain the antisense sequences of the transcripts presented on the version 2 chips. The original data was taken from the GEO database (GDS431 and GDS432). As the Affymetrix data are semiquantitative, the relative expression levels of antisense partners were analysed. We detected antisense transcription, although the average antisense expression is shifted towards smaller expression values (MGU74A version 1, 516; version 2, 1688). An inverse direct correlation between sense and antisense expression values could be observed at high expression values. At a very high relative expression—above 40,000—the Pearson correlation coefficient is getting closer to −1. Transcripts with high inverse expression ratio may be correlated to the investigated gene (major histocompatibility complex class II trans activator). The ratio of sense to antisense transcripts varied among different chromosomes; on chromosomes 14 and 1 the level of antisense expression was higher than that of sense. We conclude that antisense transcription is a common phenomenon in the mouse genome. The hypothesis of regulatory role of antisense transcripts is supported by the inverse antisense gene expression of highly expressed genes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aravin A. A., Naumova N. M., Tulin A. V., Vagin V. V., Rozovsky Y. M. and Gvozdev V. A. 2001 Double-stranded RNA-mediated silencing of genomic tandem repeats and transposable elements in the D. melanogaster germline. Curr. Biol. 11, 1017–1027
Bartel D. P. 2004 MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297
Billy E., Brondani V., Zhang H., Muller U. and Filipowicz W. 2001 Specific interference with gene expression induced by long, double-stranded RNA in mouse embryonal teratocarcinoma cell lines. Proc. Natl. Acad. Sci. USA 98, 14428–14433.
Brown C. J. and Chow J. C. 2003 Beyond sense: the role of antisense RNA in controlling Xist expression. Semin. Cell. Dev. Biol. 14, 341–347.
Carmichael G. G. 2003 Antisense starts making more sense. Nat. Biotechnol. 21, 371–372
Chang Y., Spicer D. B. and Sonenshein G. E. 1991 Effects of IL-3 on promoter usage, attenuation and antisense transcription of the c-myc oncogene in the IL-3-dependent Ba/F3 early pre-B cell line. Oncogene 6, 1979–1982.
Chen J., Sun M., Kent W. J., Huang X., Xie H., Wang W. et al. 2004 Over 20% of human transcripts might form sense-antisense pairs. Nucleic Acids Res. 32, 4812–4820.
Chen J., Sun M., Hurst L. D., Carmichael G. G. and Rowley J. D. 2005a Human antisense genes have unusually short introns: evidence for selection for rapid transcription. Trends Genet. 21, 203–207.
Chen J., Sun M., Hurst L. D., Carmichael G. G. and Rowley J. D. 2005b Genome-wide analysis of coordinate expression and evolution of human cis-encoded sense-antisense transcripts. Trends Genet. 21, 326–329.
Conrad C., Vianna C., Freeman M. and Davies P. 2002 A polymorphic gene nested within an intron of the tau gene: implications for Alzheimer’s disease. Proc. Natl. Acad. Sci. 99, 7751–7756.
Enerly E., Sheng Z. and Li K. B. 2005 Natural antisense as potential regulator of alternative initiation, splicing and termination. In Silico Biol. 5, 367–377.
Faghihi M. A. and Wahlestedt C. 2006 RNA interference is not involved in natural antisense mediated regulation of gene expression in mammals. Genome Biol. 7, R38.
Farrell C. M. and Lukens L. N. 1995 Naturally occurring antisense transcripts are present in chick embryo chondrocytes simultaneously with the down-regulation of the alpha 1 (I) collagen gene. J. Biol. Chem. 270, 3400–3408.
Hildebrandt M. and Nellen W. 1992 Differential antisense transcription from the Dictyostelium EB4 gene locus: implications on antisense-mediated regulation of mRNA stability. Cell 69, 197–204.
Hsieh-Li H. M., Witte D. P., Weinstein M., Brandford W., Li H. and Small K. 1995 Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility. Development. 121, 1373–1385.
Kampa D., Cheng J., Kapranov P., Yamanaka M., Brubaker S., Cawley S. et al. 2004 Novel RNAs identified from an in-depth analysis of the transcriptome of human chromosomes 21 and 22. Genome Res. 14, 331–342.
Katayama S., Tomaru Y., Kasukawa T., Waki K., Nakanishi M., Nakamura M. et al. RIKEN Genome Exploration Research Group, Genome Science Group (Genome Network Project Core Group), FANTOM Consortium 2005 Antisense transcription in the mammalian transcriptome. Science. 309, 1564–1566.
Kiyosawa H., Yamanaka I., Osato N., Kondo S., Hayashizaki Y., RIKEN GER Group, GSL Members and Yoshihide H. 2003 Antisense transcripts with FANTOM2 clone set and their implications for gene regulation. Genome Res. 13, 1324–1334.
Kumar M. and Carmichael G. G. 1997 Nuclear antisense RNA induces extensive adenosine modifications and nuclear retention of target transcripts. Proc. Natl. Acad. Sci. USA 94, 3542–3547.
Labrador M., Mongelard F., Plata-Rengifo P., Baxter E. M., Corces V. G. and Gerasimova T. I. 2001 Protein encoding by both DNA strands. Nature 409, 1000.
Lavorgna G., Dahary D., Lehner B., Sorek R., Sanderson C. M. and Casari G. 2004 In search of antisense. Trends Biochem. Sci. 29, 88–94.
Lee J. T. 2003 Molecular links between X-inactivation and autosomal imprinting: X-inactivation as a driving force for the evolution of imprinting? Curr. Biol. 13, 242–254.
Lee J. T., Davidow L. S. and Warshawsky D. 1999 Tsix, a gene antisense to Xist at the X-inactivation centre. Nat. Genet. 21, 400–404.
Lee J. M., Zhang S., Saha S., Santa Anna S., Jiang C. and Perkins J. 2001 RNA Expression Analysis Using an Antisense Bacillus subtilis Genome Array. J. Bacteriol. 183, 7371–7380.
Lehner B., Williams G., Campbell R. D. and Sanderson C. M. 2002 Antisense transcripts in the human genome. Trends Genet. 18, 63–65.
Levinson B., Kenwrick S., Gamel P., Fisher K. and Gitschier J. 1992 Evidence for a third transcript from the human factor VIII gene. Genomics 14, 585–589.
Li A. W. and Murphy P. R. 2000 Expression of alternatively spliced FGF-2 antisense RNA transcripts in the central nervous system: regulation of FGF-2 mRNA translation. Mol. Cell. Endocrinol. 170, 233–242.
Lipman D. J. 1997 Making (anti)sense of non-coding sequence conservation. Nucleic Acids Res. 25, 3580–3583.
Malik K. T., Wallace J. I., Ivins S. M. and Brown K. W. 1995 Identification of an antisense WT1 promoter in intron 1: implications for WT1 gene regulation. Oncogene 11, 1589–1595.
Moore T., Constancia M., Zubair M., Bailleul B., Feil R., Sasaki H. and Reik W. 1997 Multiple imprinted sense and antisense transcripts, differential methylation and tandem repeats in a putative imprinting control region upstream of mouse Igf2. Proc. Natl. Acad. Sci. USA. 94, 12509–12514.
Peters N. T., Rohrbach J. A., Zalewski B. A., Byrkett C. M. and Vaughn J. C. 2003 RNA editing and regulation of Drosophila 4f-rnp expression by sas-10 antisense readthrough mRNA transcripts. RNA 9, 698–710.
Rahman L., Bliskovski V., Reinhold W. and Zajac-Kaye M. 2002 Alternative splicing of brain-specific PTB defines a tissue-specific isoform pattern that predicts distinct functional roles. Genomics 80, 245–249.
Sleutels F., Zwart R. and Barlow D. P. 2002 The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature 415, 810–813.
Sureau A., Soret J., Guyon C., Gaillard C., Dumon S., Keller M. et al. 1997 Characterization of multiple alternative RNAs resulting from antisense transcription of the PR264/SC35 splicing factor gene. Nucleic Acids Res. 25, 4513–4522.
Thakur N., Tiwari V. K., Thomassin H., Pandey R. R., Kanduri M., Gondor A. et al. 2004 An antisense RNA regulates the bidirectional silencing property of the Kcnq1 imprinting control region. Mol. Cell. Biol. 24, 7855–7862.
Trinklein N. D., Aldred S. F., Hartman S. J., Schroeder D. I., Otillar R. P. and Myers R. M. 2004 An abundance of bidirectional promoters in the human genome. Genome Res. 14, 62–66.
Tufarelli C., Stanley J. A., Garrick D., Sharpe J. A., Ayyub H., Wood W. G. and Higgs D. R. 2003 Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease. Nat. Genet. 34, 157–165.
Wang X. J., Gaasterland T. and Chua N. H. 2005 Genome-wide prediction and identification of cis-natural antisense transcripts in Arabidopsis thaliana. Genome Biol. 6, R30.
Wong A. W., Brickey W. J., Taxman D. J., van Deventer H. W., Reed W., Gao J. X. et al. 2003 CIITA-regulated plexin-A1 affects T-cell-dendritic cell interactions. Nat. Immunol. 4, 891–898.
Yamasaki K., Joh K., Ohta T., Masuzaki H., Ishimaru T., Mukai T. et al. 2003 Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a. Hum. Mol. Genet. 12, 837–847.
Yelin R., Dahary D., Sorek R., Levanon E. Y., Goldstein O., Shoshan A. et al. 2003 Widespread occurrence of antisense transcription in the human genome. Nat. Biotechnol. 21, 379–386.
Zhang Y., Liu X. S., Liu Q. R. and Wei L. 2006 Genome-wide in silico identification and analysis of cis natural antisense transcripts (cis-NATs) in ten species. Nucleic Acids Res. 34, 3465–3475.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Györffy, A., Surowiak, P., Tulassay, Z. et al. Highly expressed genes are associated with inverse antisense transcription in mouse. J Genet 86, 103–109 (2007). https://doi.org/10.1007/s12041-007-0015-x
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12041-007-0015-x