Regulation of gene expression at the translational level is crucial for many developmental processes. eIF4E, the mRNA cap-binding protein, is a key player in regulation of translation initiation. Two to eight isoforms of eIF4E have been found in plants, flies, mammals, frogs, fish, and nematodes, yet their individual roles are poorly understood. eIF4E is represented by five isoforms in C. elegans, IFE-1 through IFE-5, which differ in cap-binding specificity, tissue and developmental expression, and requirement for viability. We investigated the role of the IFE-2 protein, which has 40% identity to the major human eIF4E isoform and 68% and 57% identity to C. elegans IFE-1 and IFE-5, respectively. IFE-2 binds both types of mRNA caps found in C. elegans, containing 2,2,7-trimethylguanosine and 7-methylguanosine, and is present in the active 48S translation initiation complexes. IFE-2 and IFE-3 are the most abundant of the five C. elegans IFEs.
ife-2::gfp is ubiquitously expressed in both males and hermaphrodites. Expression begins in embryos and remains abundant through the entire life cycle. IFE-2::GFP accumulates in pharynx, intestine, spermatheca, body wall muscle, vulva, some tail neurons, the pharyngeal nerve ring, and hypodermis. Surprisingly, worms depleted of IFE-2 do not display obvious defects under normal conditions. However, growth of the
ife-2 knockout strain at high temperatures (27C) causes maternal effect embryonic lethality. At 20C,
ife-2-deficient worms manifest a high frequency of males. We have investigated the molecular basis of these phenotypic changes by identifying the mRNAs whose translation is most affected by loss of IFE-2. Affymetrix GeneChip array analysis of
ife-2-deficient mutants showed that translational efficiency (in the absence of transcriptional changes) was significantly reduced for only 132 out of ~ 18,000 C. elegans transcripts. The
him-4 mRNA was identified among them, which could explain one of
ife-2 knockout phenotypic traits. mRNAs whose translation was reduced in
ife-2-deficient animals also encode proteins involved in environmental stress and nutrition responses. These data, as well as those for
ife-4 (see abstract by Rhoads et al.), support the idea that each C. elegans eIF4E ortholog is involved in the translation of specific subsets of mRNAs. (Supported by NIH Grant GM20818.)