Holmstrom, T.H. et al. (2008) c-Jun supports ribosomal RNA processing and nucleolar localization of RNA helicase DDX21. Journal of Biological Chemistry, 283(11), pp. 7046-7053. (doi: 10.1074/jbc.M709613200)
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Abstract
The molecular mechanisms by which the AP-1 transcription factor c-Jun exerts its biological functions are not clearly understood. In addition to its well established role in transcriptional regulation of gene expression, several reports have suggested that c-Jun may also regulate cell behavior by non-transcriptional mechanisms. Here, we report that small interfering RNA-mediated depletion of c-Jun from mammalian cells results in inhibition of 28 S and 18 S rRNA accumulation. Moreover, we show that c-Jun depletion results in partial translocation of RNA helicase DDX21, implicated in rRNA processing, from the nucleolus to the nucleoplasm. We demonstrate that DDX21 translocation is rescued by exogenous c-Jun expression and that c-Jun depletion inhibits rRNA binding of DDX21. Furthermore, the direct interaction between c-Jun and DDX21 regulates nucleolar localization of DDX21. These results demonstrate that in addition to its transcriptional effects, c-Jun regulates rRNA processing and nucleolar compartmentalization of the rRNA processing protein DDX21. Thus, our results demonstrate a nucleolar mechanism through which c-Jun can regulate cell behavior. Moreover, these results suggest that the phenotypes observed previously in c-Jun-depleted mouse models and cell lines could be partly due to the effects of c-Jun on rRNA processing.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Gillespie, Professor David |
| Authors: | Holmstrom, T.H., Mialon, A., Kallio, M., Nymalm, Y., Mannermaa, L., Holm, T., Johansson, H., Black, E., Gillespie, D., Salminen, T.A., Langel, U., Valdez, B.C., and Westermarck, J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Journal of Biological Chemistry |
| Journal Abbr.: | J Biol Chem. |
| Publisher: | American Society for Biochemistry and Molecular Biology, Inc. |
| ISSN: | 0021-9258 |
| ISSN (Online): | 1083-351X |
| Published Online: | 07 January 2008 |
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