Functional characterization of five eIF4E isoforms in Caenorhabditis elegans

Recognition of the 5'-cap structure of mRNA by eIF4E is a critical step in the recruitment of most mRNAs to the ribosome. In Caenorhabditis elegans, s imilar to 70% of mRNAs contain an unusual 2,2,7-trimethylguanosine cap stru cture as a result of trans-splicing onto the 5' end of the pre-mRNA, The ch aracterization of three eIF4E isoforms in C. elegans (IFE-1, IFE-2, and IFE -3) was reported previously. The present study describes two more eIF4E iso forms expressed in C. elegans, IFE-4 and IFE-5. We analyzed the requirement of each isoform for viability by RNA interference. IFE-3, the most closely related to mammalian eIF4E-1, binds only 7-methylguanosine caps and is ess ential for viability. In contrast, three closely related isoforms (IFE-1, I FE-2, and IFE-8) bind 2,2,7-trimethylguanosine caps and are partially redun dant, but at least one functional isoform is required for viability. IFE-4, which binds only 7-methylguanosine caps, is most closely related to an unu sual eIF4E isoform found in plants (nCBP) and mammals (4E-HP) and is not es sential for viability in any combination of IFE knockout. ife-2 ife-3 ife-4 , and ife-5 mRNAs are themselves trans-spliced to SL1 spliced leaders. ife- 1 mRNA is trans-spliced to an SL2 leader, indicating that its gene resides in a downstream position of an operon.