Cloning and characterization of 4EHP, a novel mammalian eIF4E-related cap-binding protein.
All eukaryotic mRNAs (except organellar) are capped at their 5' end. The cap structure (m7GpppN, where N is any nucleotide) is extremely important for the processing and translation of mRNA. Several cap-binding proteins that facilitate these processes have been characterized. Here we describe a novel human cytoplasmic protein that is 30% identical and 60% similar to the human translation initiation factor 4E (eIF4E). We demonstrate that this protein, named 4E Homologous Protein (4EHP), binds specifically to capped RNA in an ATP- and divalent ion-independent manner. The three-dimensional structure of 4EHP, as predicted by homology modeling, closely resembles that of eIF4E and site-directed mutagenesis analysis of 4EHP strongly suggests that it shares with eIF4E a common mechanism for cap binding. A putative function for 4EHP is discussed.
Rom
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E
Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G1Y6.
Kim
H C
HC
Gingras
A C
AC
Marcotrigiano
J
J
Favre
D
D
Olsen
H
H
Burley
S K
SK
Sonenberg
N
N
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary; D039561:Eukaryotic Initiation Factor-4E; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000378:metabolism*; D039381:RNA Cap-Binding Proteins; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism
D018076:DNA, Complementary; C112609:EIF4E2 protein, human; D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D039381:RNA Cap-Binding Proteins; D016601:RNA-Binding Proteins