Distinct roles of two eIF4E isoforms in the germline of Caenorhabditis elegans

Abstract

Germ cells use both positive and negative mRNA translational control to regulate gene expression that drives their differentiation into gametes. mRNA translational control is mediated by RNA-binding proteins, miRNAs, and translation initiation factors. We have uncovered the discrete roles of two translation initiation factor eIF4E isoforms (IFE-1 and -3) that bind m7GTP mRNA caps during C. elegans germline development. IFE-3 plays important roles in germline sex determination (GSD), where it promotes oocyte cell fate and is dispensable for spermatogenesis. IFE-3 is expressed throughout the germline, localizes to germ granules but distinct from IFE-1 and PGL-1, and facilitates oocyte growth and viability. This contrasts with the robust expression of IFE-1 in spermatocytes, the isoform that resides within P granules in spermatocytes and oocytes, and promotes late spermatogenesis. Each eIF4E is localized by its cognate eIF4E binding protein (IFE-1:PGL-1 and IFE-3:IFET-1). IFE-3 and IFET-1 regulate translation of several GSD mRNAs, but not those under control of IFE-1. Distinct mutant phenotypes, in vivo localization, and differential mRNA translation suggest independent dormant and active periods for each eIF4E isoform in the germline.