Friday AJ , Keiper BD .

Figure 1. Models of mRNA translational repression and translation initiation complexes. (a) mRNAs are translationally repressed by RBPs that bind sequence recognition motifs in the 3′UTR. Protein-protein interactions with 4EBP-eIF4E-mRNA form stable mRNP complexes that inhibit the recruitment of eIF4E-bound mRNA to eIF4G, eIF4A (an mRNA helicase), and the ribosome. (b) Model of cap-dependent translation initiation utilizing the cap-binding protein eIF4E. Cap-bound mRNAs are recruited to the 40S ribosomal subunit by association with eIF4G and PABP. Association with eIF2 and eIF3 completes the 48S preinitiation complex. (c) Model of cap-independent translation. The “short” isoform of eIF4G lacking an eIF4E-binding domain is still capable of recruiting mRNA to the 40S ribosomal subunit with eIFs by binding directly to the 5′UTR.

Figure 2. Dynamic models for selective protein synthesis in germ cells. (a) A complex mixed population of mRNAs present in germ cells of various stages is selectively recruited for translation initiation by individual eIF4 isoforms. This positive selection occurs temporally as developing cells require new protein synthesis. Corresponding mRNA becomes derepressed, and the eIF4E-mRNA complex is recruited to the cap-dependent translation initiation complex by the “long” isoform of eIF4G. Other mRNAs are recruited by cap-independent translation initiation via the short eIF4G isoform that lacks the eIF4E binding domain. Episodes of selective mRNA translation by individual eIF4 isoforms drive critical germ cell fate decisions. (b) As new protein synthesis is required for germ cell renewal, growth, and differentiation, one pathway, or circuit, is activated for the translation of a certain population of stored mRNAs. mRNP complexes reach the first “translation on/off” switch at a point where bound RBPs (including eIF4 factors) undergo remodeling that results in mRNA derepression. Derepressed mRNAs following the cap-dependent circuit use a switch involving of one of the eIF4E isoforms. Successfully activating this switch, eIF4E-bound mRNA is recruited to the initiation complex via the long eIF4G. Alternatively derepressed mRNAs following the cap-independent circuit are made available for initiation recruitment via the short eIF4G in an analogous fashion. Both cap-dependent and cap-independent recruited mRNAs then reach a node in which eIF4A and ribosomes must be bound. (Note that in C. elegans and Drosophila germ cell mRNPs, eIF4A, or a homologous helicase, has been found to be prebound.) The 40S ribosomal subunit brings with it initiator Met-tRNA bound to eIF2. This step constitutes a “rheostat” in the circuit where the volume of protein synthesis can be limited by phosphorylation of eIF2. mRNAs completing this circuit are efficiently decoded into new proteins necessary for discrete germ cell developmental events.

Akkaraju, Increase in eukaryotic initiation factor 2B activity following fertilization reflects changes in redox potential. 1991, Pubmed

Akkaraju, Increase in eukaryotic initiation factor 2B activity following fertilization reflects changes in redox potential. 1991, Pubmed
Allende, Oncogenic ras protein induces meiotic maturation of amphibian oocytes in the presence of protein synthesis inhibitors. 1988, Pubmed , Xenbase
Alves, GCN2 activation and eIF2alpha phosphorylation in the maturation of mouse oocytes. 2009, Pubmed
Amiri, An isoform of eIF4E is a component of germ granules and is required for spermatogenesis in C. elegans. 2001, Pubmed
Badura, DNA damage and eIF4G1 in breast cancer cells reprogram translation for survival and DNA repair mRNAs. 2012, Pubmed
Barnard, Differential phosphorylation controls Maskin association with eukaryotic translation initiation factor 4E and localization on the mitotic apparatus. 2005, Pubmed , Xenbase
Bauer, Overexpression of the eukaryotic translation initiation factor 4G (eIF4G-1) in squamous cell lung carcinoma. 2002, Pubmed
Berry, Germ-line tumor formation caused by activation of glp-1, a Caenorhabditis elegans member of the Notch family of receptors. 1997, Pubmed
Boag, Protection of specific maternal messenger RNAs by the P body protein CGH-1 (Dhh1/RCK) during Caenorhabditis elegans oogenesis. 2008, Pubmed
Braunstein, A hypoxia-controlled cap-dependent to cap-independent translation switch in breast cancer. 2007, Pubmed
Browning, The plant translational apparatus. 1996, Pubmed
Busada, Retinoic acid regulates Kit translation during spermatogonial differentiation in the mouse. 2015, Pubmed
Cao, Dissolution of the maskin-eIF4E complex by cytoplasmic polyadenylation and poly(A)-binding protein controls cyclin B1 mRNA translation and oocyte maturation. 2002, Pubmed , Xenbase
Carvallo, Characterization of protein synthesis initiation factor 2 from Xenopus laevis oocytes. 1988, Pubmed , Xenbase
Castro, Cyclin B/cdc2 induces c-Mos stability by direct phosphorylation in Xenopus oocytes. 2001, Pubmed , Xenbase
Chennathukuzhi, The kinesin KIF17b and RNA-binding protein TB-RBP transport specific cAMP-responsive element modulator-regulated mRNAs in male germ cells. 2003, Pubmed
Collier, The DAZL family proteins are PABP-binding proteins that regulate translation in germ cells. 2005, Pubmed , Xenbase
Contreras, Depletion of the cap-associated isoform of translation factor eIF4G induces germline apoptosis in C. elegans. 2008, Pubmed
Contreras, Cap-independent translation promotes C. elegans germ cell apoptosis through Apaf-1/CED-4 in a caspase-dependent mechanism. 2011, Pubmed
Dahanukar, Smaug, a novel RNA-binding protein that operates a translational switch in Drosophila. 1999, Pubmed
de Kretser, Male infertility. 1997, Pubmed
Derry, Regulation of poly(A)-binding protein through PABP-interacting proteins. 2006, Pubmed
Detwiler, Two zinc finger proteins, OMA-1 and OMA-2, are redundantly required for oocyte maturation in C. elegans. 2001, Pubmed
Dinkova, Translation of a small subset of Caenorhabditis elegans mRNAs is dependent on a specific eukaryotic translation initiation factor 4E isoform. 2005, Pubmed
Dworkin, Functions of maternal mRNA in early development. 1990, Pubmed
Eberhart, Meiotic cell cycle requirement for a fly homologue of human Deleted in Azoospermia. 1996, Pubmed
Ephrussi, Oskar organizes the germ plasm and directs localization of the posterior determinant nanos. 1991, Pubmed
Forbes, Nanos and Pumilio have critical roles in the development and function of Drosophila germline stem cells. 1998, Pubmed
Francis, gld-1, a tumor suppressor gene required for oocyte development in Caenorhabditis elegans. 1995, Pubmed
Franklin-Dumont, A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation in Drosophila spermatocytes. 2007, Pubmed
Friday, Spatial and temporal translational control of germ cell mRNAs mediated by the eIF4E isoform IFE-1. 2015, Pubmed
Fukuyo, Structural scaffold for eIF4E binding selectivity of 4E-BP isoforms: crystal structure of eIF4E binding region of 4E-BP2 and its comparison with that of 4E-BP1. 2011, Pubmed
Furic, eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression. 2010, Pubmed
Ghosh, Loss-of-function analysis reveals distinct requirements of the translation initiation factors eIF4E, eIF4E-3, eIF4G and eIF4G2 in Drosophila spermatogenesis. 2015, Pubmed
Gold, Haploid accumulation and translational control of phosphoglycerate kinase-2 messenger RNA during mouse spermatogenesis. 1983, Pubmed
Goodwin, Translational regulation of tra-2 by its 3' untranslated region controls sexual identity in C. elegans. 1993, Pubmed
Goodwin, Translational control of development in C. elegans. 1997, Pubmed
Groisman, CPEB, maskin, and cyclin B1 mRNA at the mitotic apparatus: implications for local translational control of cell division. 2000, Pubmed , Xenbase
Gumienny, Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. 1999, Pubmed
Harris, mTOR-dependent stimulation of the association of eIF4G and eIF3 by insulin. 2006, Pubmed
Hay, Upstream and downstream of mTOR. 2004, Pubmed
Henderson, A germline-specific isoform of eIF4E (IFE-1) is required for efficient translation of stored mRNAs and maturation of both oocytes and sperm. 2009, Pubmed
Hernández, Functional analysis of seven genes encoding eight translation initiation factor 4E (eIF4E) isoforms in Drosophila. 2005, Pubmed
Holcik, Translational control in stress and apoptosis. 2005, Pubmed
Hsu, A family business: stem cell progeny join the niche to regulate homeostasis. 2012, Pubmed
Iguchi, Expression profiling reveals meiotic male germ cell mRNAs that are translationally up- and down-regulated. 2006, Pubmed
Joshi, Characterization of mammalian eIF4E-family members. 2004, Pubmed
Keiper, Translational recruitment of Xenopus maternal mRNAs in response to poly(A) elongation requires initiation factor eIF4G-1. 1999, Pubmed , Xenbase
Keiper, Functional characterization of five eIF4E isoforms in Caenorhabditis elegans. 2000, Pubmed
Keiper, Cap-independent translation initiation in Xenopus oocytes. 1997, Pubmed , Xenbase
Keiper, Protein synthesis initiation factor 4G. 1999, Pubmed
Kelly, Chromatin silencing and the maintenance of a functional germline in Caenorhabditis elegans. 1998, Pubmed
Ko, Inhibition of ovarian cancer growth by a tumor-targeting peptide that binds eukaryotic translation initiation factor 4E. 2009, Pubmed
Kouvaraki, Activation of mTOR signaling in medullary and aggressive papillary thyroid carcinomas. 2011, Pubmed
Kraemer, NANOS-3 and FBF proteins physically interact to control the sperm-oocyte switch in Caenorhabditis elegans. 1999, Pubmed
Lee, Conserved regulation of MAP kinase expression by PUF RNA-binding proteins. 2007, Pubmed
Lodish, Translational control of protein synthesis. 1976, Pubmed
Marcotrigiano, Cocrystal structure of the messenger RNA 5' cap-binding protein (eIF4E) bound to 7-methyl-GDP. 1997, Pubmed
Marcotrigiano, X-ray studies of the messenger RNA 5' cap-binding protein (eIF4E) bound to 7-methyl-GDP. 1997, Pubmed
McCall, Requirement for DCP-1 caspase during Drosophila oogenesis. 1998, Pubmed
Messina, Differential contribution of the MTOR and MNK pathways to the regulation of mRNA translation in meiotic and postmeiotic mouse male germ cells. 2010, Pubmed
Minshall, CPEB interacts with an ovary-specific eIF4E and 4E-T in early Xenopus oocytes. 2007, Pubmed , Xenbase
Miyoshi, Discrimination between mono- and trimethylated cap structures by two isoforms of Caenorhabditis elegans eIF4E. 2002, Pubmed
MONESI, RIBONUCLEIC ACID SYNTHESIS DURING MITOSIS AND MEIOSIS IN THE MOUSE TESTIS. 1964, Pubmed
Morrison, Induction of cap-independent BiP (hsp-3) and Bcl-2 (ced-9) translation in response to eIF4G (IFG-1) depletion in C. elegans. 2014, Pubmed
Mosquera, A mRNA localized to the vegetal cortex of Xenopus oocytes encodes a protein with a nanos-like zinc finger domain. 1993, Pubmed , Xenbase
Nakamura, Drosophila cup is an eIF4E binding protein that associates with Bruno and regulates oskar mRNA translation in oogenesis. 2004, Pubmed
Newport, Regulation of the cell cycle during early Xenopus development. 1984, Pubmed , Xenbase
Nousch, Translational control in the Caenorhabditis elegans germ line. 2013, Pubmed
Otulakowski, Steroid and oxygen effects on eIF4F complex, mTOR, and ENaC translation in fetal lung epithelia. 2007, Pubmed
Patrick, Preparation and characterization of cell-free protein synthesis systems from oocytes and eggs of Xenopus laevis. 1989, Pubmed , Xenbase
Pei, MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damage sites. 2011, Pubmed
Piqué, A combinatorial code for CPE-mediated translational control. 2008, Pubmed , Xenbase
Prévôt, Conducting the initiation of protein synthesis: the role of eIF4G. 2003, Pubmed
Proud, Regulation of protein synthesis by insulin. 2006, Pubmed
Rhoads, Protein synthesis, cell growth and oncogenesis. 1991, Pubmed
Rinker-Schaeffer, Decreasing the level of translation initiation factor 4E with antisense RNA causes reversal of ras-mediated transformation and tumorigenesis of cloned rat embryo fibroblasts. 1993, Pubmed
Robalino, Two zebrafish eIF4E family members are differentially expressed and functionally divergent. 2004, Pubmed , Xenbase
Roy, The cyclin B2 component of MPF is a substrate for the c-mos(xe) proto-oncogene product. 1990, Pubmed , Xenbase
Ruggiu, The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. 1997, Pubmed
Salehi, Expression of the eukaryotic translation initiation factor 4E (eIF4E) and 4E-BP1 in esophageal cancer. 2006, Pubmed
Sengupta, Germ granules and the control of mRNA translation. 2012, Pubmed , Xenbase
Sengupta, ifet-1 is a broad-scale translational repressor required for normal P granule formation in C. elegans. 2013, Pubmed
Seydoux, Soma-germline asymmetry in the distributions of embryonic RNAs in Caenorhabditis elegans. 1994, Pubmed
Shen, eIF4A controls germline stem cell self-renewal by directly inhibiting BAM function in the Drosophila ovary. 2009, Pubmed
Silvera, Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer. 2009, Pubmed
Silvera, Inflammatory breast cancer cells are constitutively adapted to hypoxia. 2009, Pubmed
Sonenberg, The mRNA 5' cap-binding protein eIF4E and control of cell growth. 1998, Pubmed
Song, A C. elegans eIF4E-family member upregulates translation at elevated temperatures of mRNAs encoding MSH-5 and other meiotic crossover proteins. 2010, Pubmed
Spassov, The PUF family of RNA-binding proteins: does evolutionarily conserved structure equal conserved function? 2003, Pubmed
Spike, The TRIM-NHL protein LIN-41 and the OMA RNA-binding proteins antagonistically control the prophase-to-metaphase transition and growth of Caenorhabditis elegans oocytes. 2014, Pubmed
Stebbins-Boaz, Maskin is a CPEB-associated factor that transiently interacts with elF-4E. 1999, Pubmed , Xenbase
Styhler, vasa is required for GURKEN accumulation in the oocyte, and is involved in oocyte differentiation and germline cyst development. 1998, Pubmed
Subramaniam, Dedifferentiation of primary spermatocytes into germ cell tumors in C. elegans lacking the pumilio-like protein PUF-8. 2003, Pubmed
Sun, Mutation of Eif4g3, encoding a eukaryotic translation initiation factor, causes male infertility and meiotic arrest of mouse spermatocytes. 2010, Pubmed
Syntichaki, eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans. 2007, Pubmed
Tachibana, Functional dynamics of H3K9 methylation during meiotic prophase progression. 2007, Pubmed
Tadros, Setting the stage for development: mRNA translation and stability during oocyte maturation and egg activation in Drosophila. 2005, Pubmed , Xenbase
Tarun, A common function for mRNA 5' and 3' ends in translation initiation in yeast. 1995, Pubmed
Tavernarakis, Protein synthesis and aging: eIF4E and the soma vs. germline distinction. 2007, Pubmed
Tocchini, The TRIM-NHL protein LIN-41 controls the onset of developmental plasticity in Caenorhabditis elegans. 2014, Pubmed
Tomancak, Oocyte polarity depends on regulation of gurken by Vasa. 1998, Pubmed
Tomek, The "closed loop model" in controlling mRNA translation during development. 2012, Pubmed , Xenbase
Updike, Germ-granule components prevent somatic development in the C. elegans germline. 2014, Pubmed
Wakiyama, mRNA encoding the translation initiation factor eIF-4E is expressed early in Xenopus embryogenesis. 1995, Pubmed , Xenbase
Wakiyama, Analysis of the isoform of Xenopus euakryotic translation initiation factor 4E. 2001, Pubmed , Xenbase
Wilhelm, Cup is an eIF4E binding protein required for both the translational repression of oskar and the recruitment of Barentsz. 2003, Pubmed
Winkler, Multiple levels of regulation of protein synthesis at fertilization in sea urchin eggs. 1985, Pubmed
Yoon, CDC-25.1 controls the rate of germline mitotic cell cycle by counteracting WEE-1.3 and by positively regulating CDK-1 in Caenorhabditis elegans. 2012, Pubmed
Zanin, LARP-1 promotes oogenesis by repressing fem-3 in the C. elegans germline. 2010, Pubmed
Ziomek, Cell surface interaction induces polarization of mouse 8-cell blastomeres at compaction. 1980, Pubmed