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, Ülo
AU - Valdez, Benigno C.
AU - Westermarck, Jukka
PY - 2008/1/7
Y1 - 2008/1/7
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.
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000253779600049&KeyUID=WOS:000253779600049
U2 - 10.1074/jbc.M709613200
DO - 10.1074/jbc.M709613200
M3 - Article
SN - 0021-9258
VL - 283
SP - 7046
EP - 7053
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
ER -