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Identification and characterization of a noncoding RNA at the mouse Pcna locus

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Molecules and Cells

Abstract

AK007836 encodes a noncoding RNA (ncRNA) consisting of 2 exons. Since AK007836 is located just upstream of Pcna and transcribed in the opposite direction to that of Pcna, we analyzed its expression pattern. Both ncRNA and Pcna expressions were detected in in vitro and in vivo cells, showing a positive correlation. A 177 bp region separating the first exons of Pcna and AK007836 has a bidirectional promoter activity. When the expression of ncRNA was reduced by siRNA, Pcna expression was also reduced in normal cells, but not in cancer cells. These results suggest that the ncRNA is divergently transcribed from the bidirectional promoter, positively regulating the neighboring protein-coding Pcna gene transcription, and this regulatory function is somehow disrupted in cancer cells.

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References

  • Alder, H., Yoshinouchi, M., Prystowsky, M.B., Appasamy, M.P., and Baserga, R. (1992). A conserved region in intron 1 negatively regulates the expression of the PCNA gene. Nucleic Acids Res. 20, 1769–1775.

    Article  PubMed  CAS  Google Scholar 

  • An, S., and Song, J.J. (2011). The coded functions of noncoding RNAs for gene regulation. Mol. Cells 31, 491–496.

    Article  PubMed  CAS  Google Scholar 

  • Baserga, R. (1991). Growth regulation of the PCNA gene. J. Cell Sci. 98, 433–436.

    PubMed  CAS  Google Scholar 

  • Carninci, P. (2010). RNA dust: where are the genes? DNA Res. 17, 51–59.

    Article  PubMed  CAS  Google Scholar 

  • Chang, C.D., Ottavio, L., Travali, S., Lipson, K.E., and Baserga, R. (1990). Transcriptional and posttranscriptional regulation of the proliferating cell nuclear antigen gene. Mol. Cell. Biol. 10, 3289–3296.

    PubMed  CAS  Google Scholar 

  • Costa, F.F. (2005). Non-coding RNAs: new players in eukaryotic biology. Gene 357, 83–94.

    Article  PubMed  CAS  Google Scholar 

  • Costa, F.F. (2010). Non-coding RNAs: meet thy masters. Bioessays 32, 599–608.

    Article  PubMed  CAS  Google Scholar 

  • Engström, P.G., Suzuki, H., Ninomiya, N., Akalin, A., Sessa, L., Lavorgna, G., Brozzi, A., Luzi, L., Tan, S.L., Yang, L., et al. (2006). Complex Loci in human and mouse genomes. PLoS Genet. 2, e47.

    Article  PubMed  Google Scholar 

  • Feng, J., Bi, C., Clark, B.S., Mady, R., Shah, P., and Kohtz, J.D. (2006). The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Genes Dev. 20, 1470–1484.

    Article  PubMed  CAS  Google Scholar 

  • Han, J., Kim, D., and Morris, K.V. (2007). Promoter-associated RNA is required for RNA-directed transcriptional gene silencing in human cells. Proc. Natl. Acad. Sci. USA 104, 12422–12427.

    Article  PubMed  CAS  Google Scholar 

  • Jaskulski, D., Gatti, C., Travali, S., Calabretta, B., and Baserga, R. (1988). Regulation of the proliferating cell nuclear antigen cyclin and thymidine kinase mRNA levels by growth factors. J. Biol. Chem. 263, 10175–10179.

    PubMed  CAS  Google Scholar 

  • Lanz, R.B., McKenna, N.J., Onate, S.A., Albrecht, U., Wong, J., Tsai, S.Y., Tsai, M.J., and O’Malley, B.W. (1999). A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell 97, 17–27.

    Article  PubMed  CAS  Google Scholar 

  • Maga, G., and Hubscher, U. (2003). Proliferating cell nuclear antigen (PCNA): a dancer with many partners. J. Cell Sci. 116, 3051–3060.

    Article  PubMed  CAS  Google Scholar 

  • Matsuoka, S., Yamaguchi, M., Hayashi, Y., and Matsukage, A. (1993). Nucleotide sequence and promoter-specific effect of a negative regulatory region located upstream of the mouse proliferating cell nuclear antigen gene. Eur. J. Biochem. 218, 173–181.

    Article  PubMed  CAS  Google Scholar 

  • Morris, K.V., Santoso, S., Turner, A.M., Pastori, C., and Hawkins, P.G. (2008). Bidirectional transcription directs both transcriptional gene activation and suppression in human cells. PLoS Genet. 4, e1000258.

    Article  PubMed  Google Scholar 

  • Ørom, U.A., Derrien, T., Beringer, M., Gumireddy, K., Gardini, A., Bussotti, G., Lai, F., Zytnicki, M., Notredame, C., Huang, Q., et al. (2010). Long noncoding RNAs with enhancer-like function in human cells. Cell 143, 46–58.

    Article  PubMed  Google Scholar 

  • Osato, N., Suzuki, Y., Ikeo, K., and Gojobori, T. (2007). Transcriptional interferences in cis natural antisense transcripts of humans and mice. Genetics 176, 1299–1306.

    Article  PubMed  CAS  Google Scholar 

  • Ottavio, L., Chang, C.D., Rizzo, M.G., Travali, S., Casadevall, C., and Baserga, R. (1990). Importance of introns in the growth regulation of mRNA levels of the proliferating cell nuclear antigen gene. Mol. Cell. Biol.10, 303–309.

    PubMed  CAS  Google Scholar 

  • Pietrzkowski, Z., Alder, H., Chang, C.D., Ku, D.H., and Baserga, R. (1991). Characterization of an enhancer-like structure in the promoter region of the proliferating cell nuclear antigen (PCNA) gene. Exp. Cell Res. 193, 283–290.

    Article  PubMed  CAS  Google Scholar 

  • Ponting, C.P., Oliver, P.L., and Reik, W. (2009). Evolution and functions of long noncoding RNAs. Cell 136, 629–641.

    Article  PubMed  CAS  Google Scholar 

  • Preker, P., Nielsen, J., Kammler, S., Lykke-Andersen, S., Christensen, M.S., Mapendano, C.K., Schierup, M.H., and Jensen, T.H. (2008). RNA exosome depletion reveals transcription upstream of active human promoters. Science 322, 1851–1854.

    Article  PubMed  CAS  Google Scholar 

  • Rizzo, M.G., Ottavio, L., Travali, S., Chang, C.D., Kaminska, B., and Baserga, R. (1990). The promoter of the human prolifera-ting cell nuclear antigen (PCNA) gene is bidirectional. Exp. Cell Res.188, 286–293.

    Article  PubMed  CAS  Google Scholar 

  • Seila, A.C., Calabrese, J.M., Levine, S.S., Yeo, G.W., Rahl, P.B., Flynn, R.A., Young, R.A., and Sharp, P.A. (2008). Divergent transcription from active promoters. Science 322, 1849–1851.

    Article  PubMed  CAS  Google Scholar 

  • Shamovsky, I., Ivannikov, M., Kandel, E.S., Gershon, D., and Nudler, E. (2006). RNA-mediated response to heat shock in mammalian cells. Nature 440, 556–560.

    Article  PubMed  CAS  Google Scholar 

  • Taft, R.J., Glazov, E.A., Cloonan, N., Simons, C., Stephen, S., Faulkner, G.J., Lassmann, T., Forrest, A.R., Grimmond, S.M., Schroder, K., et al. (2009) Tiny RNAs associated with transcription start sites in animals. Nat. Genet. 41, 572–578.

    Article  PubMed  CAS  Google Scholar 

  • Tommasi, S., and Pfeifer, G.P. (1999). In vivo structure of two divergent promoters at the human PCNA locus. J. Biol. Chem. 274, 27829–27838.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Wilusz, J.E., Sunwoo, H., and Spector, D.L. (2009). Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 23, 1494–1504.

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi, M., Hayashi, Y., Hirose, F., Matsuoka, S., Moriuchi, T., Shiroishi, T., Moriwaki, K., and Matsukage, A. (1991). Molecular cloning and structural analysis of mouse gene and pseudo-genes for proliferating cell nuclear antigen. Nucleic Acids Res. 19, 2403–2410.

    Article  PubMed  CAS  Google Scholar 

  • Zerler, B., Roberts, R.J., Mathews, M.B., and Moran, E. (1987). Different functional domains of the adenovirus E1A gene are involved in regulation of host cell cycle products. Mol. Cell. Biol. 7, 821–829.

    PubMed  CAS  Google Scholar 

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Correspondence to Myoung Hee Kim.

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These authors contributed equally to this work.

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Lee, JY., Khan, A.A., Min, H. et al. Identification and characterization of a noncoding RNA at the mouse Pcna locus. Mol Cells 33, 111–116 (2012). https://doi.org/10.1007/s10059-012-2164-x

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  • DOI: https://doi.org/10.1007/s10059-012-2164-x

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