A C. elegans eIF4E-family member upregulates translation at elevated temperatures of mRNAs

Introduction Initiation of translation in eukaryotes requires the action of at least 33 polypeptides constituting the canonical initiation factors, which act to assemble a series of complexes of increasing size: 43S, 48S and 80S (Kapp and Lorsch, 2004). The rate-limiting step under normal conditions is binding of mRNA to the 43S pre-initiation complex to form the 48S pre-initiation complex. Efficient recruitment of mRNA requires a 5 -terminal 7-methylguanosinecontaining cap, which inserts into a narrow pocket in eukaryotic initiation factor (eIF) 4E (Marcotrigiano et al., 1997; Matsuo et al., 1997). For cap binding to lead to productive translational initiation, eIF4E must also bind to eIF4G, which occurs with high affinity on the opposite side of eIF4E (Marcotrigiano et al., 1999). eIF4E can also bind to proteins other than eIF4G, the first discovered being the 4E-BPs: 4E-BP-1, -2 and -3 (Gingras et al., 2004). eIF4G and the 4E-BPs contain a consensus sequence motif necessary for their interaction with eIF4E, YxxxxL , where X is any amino acid and is L, M or F. Because their binding is mutually exclusive, the 4E-BPs sequester eIF4E from eIF4G and the 48S pre-initiation complex, thereby inhibiting translation. The number of known eIF4E-binding partners that utilize the YxxxxL motif has now grown to at least 15 (Rhoads, 2009). Interaction with some of these binding partners has revealed new physiological roles for eIF4E. For instance, an eIF4E-binding protein, Maskin, participates in mRNA-specific translational repression through interaction with the cytoplasmic polyadenylation element-binding protein (Richter, 2008). Nearly all eukaryotes examined to date express multiple eIF4Efamily members (Joshi et al., 2005). Physiological roles for the different eIF4E-family members within a single organism are beginning to emerge. For instance, 4EHP, one of seven eIF4Efamily members expressed in Drosophila, specifically interacts with Bicoid to suppress caudal mRNA translation in the anterior region of the embryo (Cho et al., 2005). Translation of hunchback mRNA also is regulated by 4EHP, but its binding partner is Brat (Cho et al., 2006). The Xenopus oocyte-specific family member eIF4E-1B represses translation early in oogenesis when Maskin is absent by binding 4E-T and regulating the timing of maturation (Evsikov and Marin de Evsikova, 2009; Minshall et al., 2007). Five eIF4E-family members are expressed in Caenorhabditis elegans, IFE-1 to IFE-5 (Jankowska-Anyszka et al., 1998; Keiper et al., 2000). RNAi experiments revealed that only IFE-3 is essential for viability. Three closely related family members, IFE-1, -2 and 5, are partially redundant since at least one is required for viability, whereas IFE-4 is not essential for viability in any combination of IFE knockdown (Keiper et al., 2000). IFE-1 is enriched in the germ line and binds to PGL-1, which localizes IFE-1 to P granules (Amiri et al., 2001). Depletion of IFE-1 by RNA interference (RNAi) shows it is required for spermatogenesis in both hermaphrodites and males (Amiri et al., 2001). Disruption of the ife-1 gene causes spermatocytes A C. elegans eIF4E-family member upregulates translation at elevated temperatures of mRNAs encoding MSH-5 and other meiotic crossover proteins