c-Jun supports ribosomal RNA processing and nucleolar localization of RNA helicase DDX21.
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.
Holmström
Tim H
TH
Centre for Biotechnology, University of Turku and Abo Akademi University, 20520 Turku, Finland.
Mialon
Antoine
A
Kallio
Marko
M
Nymalm
Yvonne
Y
Mannermaa
Leni
L
Holm
Tina
T
Johansson
Henrik
H
Black
Elizabeth
E
Gillespie
David
D
Salminen
Tiina A
TA
Langel
Ulo
U
Valdez
Benigno C
BC
Westermarck
Jukka
J
D000818:Animals; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D005347:Fibroblasts; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D012335:RNA, Ribosomal / Q000378:metabolism*
D010455:Peptides; D016755:Proto-Oncogene Proteins c-jun; D012335:RNA, Ribosomal; C528957:DDX21 protein, mouse; C501726:DDX21 protein, human; D053487:DEAD-box RNA Helicases