THE DISTINCT ROLES OF TWO eIF4E ISOFORMS AND THEIR COGNATE 4EIPS IN THE GERMLINE OF C. elegans

Abstract

Biological information becomes functional at the step of mRNA translation when the protein product is synthesized. Translational regulation of mRNAs is critically important for proper modulation of gene expression in germ cells, gametes, and embryos. The ability of the nucleus to control gene expression in these systems may be limited due to spatial or temporal constraints, as well as the breadth of gene products they express to prepare for the rapid development that follows. During development, germ granules are hubs of post-transcriptional regulation of mRNAs. They assemble and remodel messenger ribonucleoprotein (mRNP) complexes that control translational repression and activation. Recently, mRNPs have been appreciated as discrete regulatory units, whose function is dictated by the many positive and negative acting factors within the complex. Repressed mRNPs must be remodeled and activated for translation on ribosomes to introduce novel proteins into germ cells. The eIF4E:eIF4Einteracting protein (4EIP) node controls many aspects of mRNP fate including localization, stability, poly(A)-elongation, deadenylation, and translational activation/repression. Furthermore, plant and animal species have evolved to express multiple functionally distinct eIF4E and 4EIP variants within germ cells, giving rise to different modes of translational regulation. Here we investigate the physiological and translational functions of two distinct eIF4E isoforms, IFE-1 and IFE-3, and their cognate 4EIPs (PGL-1 and IFET-1 respectively) in the germline of the nematode C. elegans. We find that deficiencies in IFE-1 and IFE-3 result in unique terminal phenotypes, suggesting non-redundant functions of these two closely related proteins. Each isoform contributes to development by regulating the translation of a unique pool of mRNAs. We provide biochemical evidence that IFE-1 and IFE-3 reside in discrete mRNPs with their cognate 4EIPs, that have P granule and P body related functions respectively. Additionally, we find that these 4EIPs control the localization of their respective eIF4E and likely their differential translational functions.