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Functional analysis of
seven genes encoding eight translation initiation factor 4E (eIF4E) isoforms
in Drosophila.
Hernandez G, Altmann M, Sierra JM, Urlaub H, del Corral
RD, Schwartz P, Rivera-Pomar R.
Max-Planck-Institut fur biophysikalische Chemie, Abt.
Molekulare Biologie, Am Fassberg 11, Gottingen 37077, Germany. hgreco[at]gwdg.de
The Drosophila genome-sequencing project has revealed
a total of seven genes encoding eight eukaryotic initiation factor 4E
(eIF4E) isoforms. Four of them (eIF4E-1,2, eIF4E-3, eIF4E-4 and eIF4E-5)
share exon/intron structure in their carboxy-terminal part and form a
cluster in the genome. All eIF4E isoforms bind to the cap (m7GpppN) structure.
All of them, except eIF4E-6 and eIF4E-8 were able to interact with Drosophila
eIF4G or eIF4E-binding protein (4E-BP). eIF4E-1, eIF4E-2, eIF4E-3, eIF4E-4
and eIF4E-7 rescued a yeast eIF4E-deficient mutant in vivo. Only eIF4E-1
mRNAs and, at a significantly lower level, eIF4E3 and eIF4E-8 are expressed
in embryos and throughout the life cycle of the fly. The transcripts of
the remaining isoforms were detected from the third instar larvae onwards.
This indicates the cap-binding activity relies mostly on eIF4E-1 during
embryogenesis. This agrees with the proteomic analysis of the eIF4F complex
purified from embryos and with the rescue of l(3)67Af, an embryonic lethal
mutant for the eIF4E-1,2 gene, by transgenic expression of eIF4E-1. Overexpression
of eIF4E-1 in wild-type embryos and eye imaginal discs results in phenotypic
defects in a dose-dependent manner.
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