title: c-Jun supports ribosomal RNA processing and nucleolar localization of RNA helicase DDX21.
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.
authors.affiliation: Centre for Biotechnology, University of Turku and Abo Akademi University, 20520 Turku, Finland.
authors.forename: Tim H
authors.initials: TH
authors.lastname: Holmström
authors.forename: Antoine
authors.initials: A
authors.lastname: Mialon
authors.forename: Marko
authors.initials: M
authors.lastname: Kallio
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Nymalm
authors.forename: Leni
authors.initials: L
authors.lastname: Mannermaa
authors.forename: Tina
authors.initials: T
authors.lastname: Holm
authors.forename: Henrik
authors.initials: H
authors.lastname: Johansson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Black
authors.forename: David
authors.initials: D
authors.lastname: Gillespie
authors.forename: Tiina A
authors.initials: TA
authors.lastname: Salminen
authors.forename: Ulo
authors.initials: U
authors.lastname: Langel
authors.forename: Benigno C
authors.initials: BC
authors.lastname: Valdez
authors.forename: Jukka
authors.initials: J
authors.lastname: Westermarck
mesh_terms: 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*
chemical_list: D010455:Peptides; D016755:Proto-Oncogene Proteins c-jun; D012335:RNA, Ribosomal; C528957:DDX21 protein, mouse; C501726:DDX21 protein, human; D053487:DEAD-box RNA Helicases