Identification of FUSE-binding protein 1 as a regulatory mRNA-binding protein that represses nucleophosmin translation.
Nucleophosmin (NPM/B23) is a multifunctional oncoprotein whose protein expression levels dictate cellular growth and proliferation rates. NPM is translationally responsive to hyperactive mammalian target of rapamycin (mTOR) signals, but the mechanism of this regulation is not understood. Using chimeric translational reporters, we found that the 3' untranslated region (UTR) of the NPM messenger (m)RNA is sufficient to mediate its translational modulation by mTOR signalling. We show that far upstream element (FUSE)-binding protein 1 (FBP1) interacts specifically with the 3' UTR of NPM to repress translation. Overexpression of FBP1 resulted in translational repression of NPM mRNAs, whereas depletion of FBP1 caused a dramatic increase in NPM translation and resulted in enhanced overall cell proliferation. Thus, we propose that FBP1 is a key regulator of cell growth and proliferation through its ability to selectively bind the NPM 3' UTR and repress NPM translation.
Olanich
M E
ME
BRIGHT Institute, Washington University School of Medicine, St Louis, MO 63110, USA.
Moss
B L
BL
Piwnica-Worms
D
D
Townsend
R R
RR
Weber
J D
JD
D020121:5' Untranslated Regions; D048708:Cell Growth Processes / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D000090243:Nucleophosmin; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D020123:Sirolimus / Q000378:metabolism
D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; C492258:FUBP1 protein, human; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000090243:Nucleophosmin; D004265:DNA Helicases; D020123:Sirolimus
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