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)

Research output: Contribution to journalArticleScientificpeer-review

27 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

Fingerprint

RNA Helicases
Ribosomal RNA
Processing
Cells
Transcription Factor AP-1
Gene Expression Regulation
Small Interfering RNA
Gene expression
Phenotype
Cell Line
Proteins

Keywords

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

Cite this

Holmström, T. H., Mialon, A., Kallio, M., Nymalm, Y., Mannermaa, L., Holm, T., ... 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
Holmström, Tim H. ; Mialon, Antoine ; Kallio, Marko ; Nymalm, Yvonne ; Mannermaa, Leni ; Holm, Tina ; Johansson, Henrik ; Black, Elizabeth ; Gillespie, David ; Salminen, Tiina A. ; Langel, Ulo ; Valdez, Benigno ; Westermarck, Jukka. / C-jun supports ribosomal RNA processing and nucleolar localization of RNA helicase DDX21. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 11. pp. 7046-7053.
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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.",
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author = "Holmstr{\"o}m, {Tim H.} and Antoine Mialon and Marko Kallio and Yvonne Nymalm and Leni Mannermaa and Tina Holm and Henrik Johansson and Elizabeth Black and David Gillespie and Salminen, {Tiina A.} and Ulo Langel and Benigno Valdez and Jukka Westermarck",
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Holmström, TH, Mialon, A, Kallio, M, Nymalm, Y, Mannermaa, L, Holm, T, Johansson, H, Black, E, Gillespie, D, Salminen, TA, Langel, U, Valdez, B & Westermarck, J 2008, 'C-jun supports ribosomal RNA processing and nucleolar localization of RNA helicase DDX21', Journal of Biological Chemistry, vol. 283, no. 11, pp. 7046-7053. https://doi.org/10.1074/jbc.M709613200

C-jun supports ribosomal RNA processing and nucleolar localization of RNA helicase DDX21. / Holmström, Tim H.; Mialon, Antoine; Kallio, Marko; Nymalm, Yvonne; Mannermaa, Leni; Holm, Tina; Johansson, Henrik; Black, Elizabeth; Gillespie, David; Salminen, Tiina A.; Langel, Ulo; Valdez, Benigno; Westermarck, Jukka (Corresponding Author).

In: Journal of Biological Chemistry, Vol. 283, No. 11, 2008, p. 7046-7053.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - C-jun supports ribosomal RNA processing and nucleolar localization of RNA helicase DDX21

AU - Holmström, Tim H.

AU - Mialon, Antoine

AU - Kallio, Marko

AU - Nymalm, Yvonne

AU - Mannermaa, Leni

AU - Holm, Tina

AU - Johansson, Henrik

AU - Black, Elizabeth

AU - Gillespie, David

AU - Salminen, Tiina A.

AU - Langel, Ulo

AU - Valdez, Benigno

AU - Westermarck, Jukka

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - c-Jun

KW - AP-1 transcription

KW - gene transcription

KW - transcription factors

KW - cancer cells

KW - cell behavior

KW - protein expression

KW - proteins

KW - DDX21

KW - gene expression

U2 - 10.1074/jbc.M709613200

DO - 10.1074/jbc.M709613200

M3 - Article

VL - 283

SP - 7046

EP - 7053

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 11

ER -