AC. eleganseIF4E-family member upregulates translation at elevated temperatures of mRNAs encoding MSH-5 and other meiotic crossover proteins

Abstract

SummaryCaenorhabditis elegans expresses five family members of the translation initiation factor eIF4E whose individual physiological roles are only partially understood. We report a specific role for IFE-2 in a conserved temperature-sensitive meiotic process. ife-2 deletion mutants have severe temperature-sensitive chromosome-segregation defects. Mutant germ cells contain the normal six bivalents at diakinesis at 20°C but 12 univalents at 25°C, indicating a defect in crossover formation. Analysis of chromosome pairing in ife-2 mutants at the permissive and restrictive temperatures reveals no defects. The presence of RAD-51-marked early recombination intermediates and 12 well condensed univalents indicate that IFE-2 is not essential for formation of meiotic double-strand breaks or their repair through homologous recombination but is required for crossover formation. However, RAD-51 foci in ife-2 mutants persist into inappropriately late stages of meiotic prophase at 25°C, similar to mutants defective in MSH-4/HIM-14 and MSH-5, which stabilize a critical intermediate in crossover formation. In wild-type worms, mRNAs for msh-4/him-14 and msh-5 shift from free messenger ribonucleoproteins to polysomes at 25°C but not in ife-2 mutants, suggesting that IFE-2 translationally upregulates synthesis of MSH-4/HIM-14 and MSH-5 at elevated temperatures to stabilize Holliday junctions. This is confirmed by an IFE-2-dependent increase in MSH-5 protein levels.

Translational Control in the Caenorhabditis elegans Germ Line

“…IFE-2 has an even more de fi ned role. It regulates meiosis in hermaphrodites, because ife-2 mutants display severe chromosome segregation defects at elevated temperature (Song et al 2010 ) . Both factors have in common that they are important for ef fi cient translation of speci fi c mRNA subsets.…”

Eukaryotic initiation factor 4E-3 is essential for meiotic chromosome segregation, cytokinesis and male fertility in Drosophila

“…This suggests that a ubiquitous eIF4E isoform might carry out global translation initiation, whereas the other isoforms might be involved in more specific processes of translation (Hernández and VazquezPianzola, 2005). Work in C. elegans supports this, as IFE-1, a germline-specific eIF4E, is required for sperm (Amiri et al, 2001;Kawasaki et al, 2011) and oocyte (Henderson et al, 2009) maturation, loss of IFE-2 affects chromosome segregation at meiosis (Song et al, 2010), and IFE-4 is involved in translating only a small set of neural and muscle mRNAs involved in egg laying (Dinkova et al, 2005).…”

“…Work in other organisms also supports functions for alternative forms of eIF4E and eIF4G in the germline. It is noteworthy that IFE-2, an alternative eIF4E in C. elegans, has, like Drosophila eIF4E-3, been linked to chromosome segregation at meiosis (Song et al, 2010). This degree of evolutionary conservation suggests an ancient translational mechanism for control of this process in sperm development.…”

Spatial and temporal translational control of germ cell mRNAs mediated by the eIF4E isoform IFE-1

“…Five isoforms of eIF4E (IFE-1-IFE-5) are expressed in the nematode C. elegans (Jankowska- Anyszka et al, 1998;Keiper et al, 2000). We have previously shown that individual isoforms regulate a unique subset of mRNAs in a tissue-specific manner (Amiri et al, 2001;Dinkova et al, 2005;Henderson et al, 2009;Kawasaki et al, 2011;Song et al, 2010). Given that all IFEs bind to mRNA caps, these findings suggest a selective cap-dependent regulation that goes beyond mTOR regulation.…”