C-jun supports ribosomal RNA processing and nucleolar localization of RNA helicase DDX21

Tim H. Holmström, Antoine Mialon, Marko Kallio, Yvonne Nymalm, Leni Mannermaa, Tina Holm, Henrik Johansson, Elizabeth Black, David Gillespie, Tiina A. Salminen, Ulo Langel, Benigno Valdez, Jukka Westermarck (Corresponding Author)

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29 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)7046-7053
JournalJournal of Biological Chemistry
Volume283
Issue number11
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Keywords

  • c-Jun
  • AP-1 transcription
  • gene transcription
  • transcription factors
  • cancer cells
  • cell behavior
  • protein expression
  • proteins
  • DDX21
  • gene expression

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    Holmström, 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., & Westermarck, J. (2008). C-jun supports ribosomal RNA processing and nucleolar localization of RNA helicase DDX21. Journal of Biological Chemistry, 283(11), 7046-7053. https://doi.org/10.1074/jbc.M709613200