Gene Fusion and Overlapping Reading Frames in the Mammalian Genes for 4E-BP3 and MASK

4E-BP3 is a member of the eukaryotic initiation factor (eIF) 4F-binding protein family of translational repressors. eIF4E-binding proteins (4E-BPs) inhibit translation initiation by sequestering eIF4E, the cap-binding protein, from eIF4G thus preventing ribosome recruitment to the mRNA. Previous analysis of 4E-BP3 expression uncovered an 8.5-kb mRNA variant of unknown origin. To study this splice variant, we determined the structure of the genomic locus encoding human 4E-BP3 (EIF4EBP3). EIF4EBP3 is located on human chromosome 5q31.3 and comprises three exons (A, B, and C) and two introns. Exon B contains the region of the open reading frame responsible for eIF4E binding. GenBank™ searches revealed multiple expressed sequence tags originating from the alternative splicing of exon B with unidentified upstream exons. Further studies revealed that the 8.5-kb transcript arises from the fusion of EIF4EBP3 with the mammalian homologue of Drosophila is for and the open reading frame of the transcript is from that of that exon B is an alternative reading fusion to that of and EIF4EBP3 for the of an alternative reading frame is for two and of the of mammalian and for the analysis of 4E-BP3 and eIF4E and of the a for the fusion 4E-BP3 is a member of the eukaryotic initiation factor (eIF) 4F-binding protein family of translational repressors. eIF4E-binding proteins (4E-BPs) inhibit translation initiation by sequestering eIF4E, the cap-binding protein, from eIF4G thus preventing ribosome recruitment to the mRNA. Previous analysis of 4E-BP3 expression uncovered an 8.5-kb mRNA variant of unknown origin. To study this splice variant, we determined the structure of the genomic locus encoding human 4E-BP3 (EIF4EBP3). EIF4EBP3 is located on human chromosome 5q31.3 and comprises three exons (A, B, and C) and two introns. Exon B contains the region of the open reading frame responsible for eIF4E binding. GenBank™ searches revealed multiple expressed sequence tags originating from the alternative splicing of exon B with unidentified upstream exons. Further studies revealed that the 8.5-kb transcript arises from the fusion of EIF4EBP3 with the mammalian homologue of Drosophila is for and the open reading frame of the transcript is from that of that exon B is an alternative reading fusion to that of and EIF4EBP3 for the of an alternative reading frame is for two and of the of mammalian and for the analysis of 4E-BP3 and eIF4E and of the a for the fusion of translation is an to the initiation the is to the mRNA of recruitment is by the structure is on eukaryotic structure is by eukaryotic initiation factor (eIF) initiation reading sequence reading of protein initiation reading sequence reading of protein a of three eIF4E, the cap-binding a and a that a the ribosome and mRNA eIF4E a translational initiation and is multiple and the of the eIF4E-binding proteins inhibit translation initiation by preventing the of eIF4E with and thus ribosome to the mRNA the the eIF4G and for eIF4E of the to eIF4E is by of with eIF4E, the with on 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