Pumilio 2 controls translation by competing with eIF4E for 7-methyl guanosine cap recognition.
Pumilio 2 (Pum2) interacts with the 3' UTR-containing pumilio binding element (PBE) of RINGO/SPY mRNA to repress translation in Xenopus oocytes. Here, we show that Pum2 also binds directly to the 5' 7mG cap structure; in so doing, it precludes eIF4E from binding the cap. Using deletion analysis, we have mapped the cap interaction domain of Pum2 to the amino terminus of the protein and identified a conserved tryptophan residue that mediates this specific interaction. Reporter mRNA-based assays demonstrate that Pum2 requires the conserved tryptophan to repress translation in injected Xenopus oocytes. Thus, in addition to its suggested role in regulating poly(A) tail length and mRNA stability, our results suggest that vertebrate Pumilio can repress translation by blocking the assembly of the essential initiation complex on the cap.
Cao
Quiping
Q
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Padmanabhan
Kiran
K
Richter
Joel D
JD
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002478:Cells, Cultured; D039561:Eukaryotic Initiation Factor-4E / Q000737:chemistry / Q000378:metabolism*; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D014176:Protein Biosynthesis / Q000235:genetics; D012315:RNA Caps / Q000378:metabolism*; D020871:RNA Stability / Q000502:physiology; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D014982:Xenopus laevis
D039561:Eukaryotic Initiation Factor-4E; C508296:Pum2 protein, Xenopus; D012315:RNA Caps; D016601:RNA-Binding Proteins; D029867:Xenopus Proteins; D006151:Guanosine; C016578:7-methylguanosine