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

Abstract

Regulated mRNA translation is vital for germ cells to produce new proteins in the spatial and temporal patterns that drive gamete development. Translational control involves the de-repression of stored mRNAs and their recruitment by eukaryotic initiation factors (eIFs) to ribosomes. C. elegans expresses five eIF4Es (IFE-1-IFE-5); several have been shown to selectively recruit unique pools of mRNA. Individual IFE knockouts yield unique phenotypes due to inefficient translation of certain mRNAs. Here, we identified mRNAs preferentially translated through the germline-specific eIF4E isoform IFE-1. Differential polysome microarray analysis identified 77 mRNAs recruited by IFE-1. Among the IFE-1-dependent mRNAs are several required for late germ cell differentiation and maturation. Polysome association of gld-1, vab-1, vpr-1, rab-7 and rnp-3 mRNAs relies on IFE-1. Live animal imaging showed IFE-1-dependent selectivity in spatial and temporal translation of germline mRNAs. Altered MAPK activation in oocytes suggests dual roles for IFE-1, both promoting and suppressing oocyte maturation at different stages. This single eIF4E isoform exerts positive, selective translational control during germ cell differentiation.

Regulation of Germ Cell mRNPs by eIF4E:4EIP Complexes: Multiple Mechanisms, One Goal

“…A model has emerged in which eIF4 factors reside in such mRNPs in both their repressed and active states ( Figure 1 ). Data from metazoan and plant developmental systems are consistent with this model showing multiple eIF4 group members participate in mRNP remodeling and coordinate activation/repression switches that drive selective mRNA translation ( Stebbins-Boaz et al, 1999 ; Yoffe et al, 2006 ; Mayberry et al, 2009 ; Hernandez et al, 2013 ; Mitchell and Parker, 2014 ; Morrison et al, 2014 ; Friday and Keiper, 2015 ; Friday et al, 2015 ; Lee et al, 2015 ; Huggins et al, 2020 ). This review focuses on known roles for isoforms of the mRNA cap-binding protein eIF4E, and cognate binding partners, the eIF4E-interacting proteins (4EIPs) in regulating mRNP localization, storage, turnover, and translational activation in germ cells and embryos ( Figure 1 ).…”

“…In C. elegans , multiple eIF4E isoforms (IFE-1 – IFE-5) are expressed in a tissue specific manner and each has unique developmental functions ( Keiper et al, 2000 ; Amiri et al, 2001 ; Dinkova et al, 2005 ; Song et al, 2010 ). The two major germ cell isoforms, IFE-1 and IFE-3, have distinct roles in translational regulation of unique subsets of mRNAs ( Henderson et al, 2009 ; Friday et al, 2015 ; Huggins et al, 2020 ). By measuring translation of mRNAs in worms lacking either IFE-1 or IFE-3, it was found that IFE-1 is critical for translating specific mRNAs related to oocyte maturation ( pos -1, vab -1, mex -1) and mRNAs involved in spermatocyte cytokinesis ( Henderson et al, 2009 ; Friday et al, 2015 ).…”

“…This review seeks to outline the contribution of eIF4E:4EIP complexes in germ cells and embryos that control translational repression/activation switches. Such switches are vital for the progression of germ cells throughout meiosis, for example ( Friday et al, 2015 ; Lee et al, 2015 ). For clarity, the nomenclature 4E-interacting protein (4EIP) is used for all eIF4E-sequestering proteins other than the canonical 4EBPs 1 and 2 that are released upon phosphorylation by mTOR kinase.…”

Positive mRNA Translational Control in Germ Cells by Initiation Factor Selectivity

“…Follow-up studies showed that IFE-1 promotes germ cell development and preparation for embryogenesis by positively recruiting critical mRNAs for steps in each process (e.g., mex-1, oma-1, glp-1, gld-1, pos-1, pal-1, vab-1, rab-7, ran-1, and rnp-3 ) [ 63 , 100 ]. Selective translational recruitment by IFE-1 has been demonstrated in situ in live worms as mRNAs become activated in a temporal and spatial manner within individual germ cells [ 100 ]. Another germ cell eIF4E (IFE-3) is expressed in the same oocyte stages as IFE-1, but its subcellular localization differs.…”

eIF4E and Interactors from Unicellular Eukaryotes

“…This is due to different life stages requiring particular reprogramming of expressed proteins. As mentioned, different variants of eIF4E in conjunction with partner 4E-BPs also help to regulate mRNA selection under differing developmental conditions in multicellular eukaryotic organisms [1][2][3][4][5][6][7][8][9][10][11][12]. As mainly post-transcriptional regulation of gene expression exists for protozoans, it may require variations of initiation factors to favor expression of certain stage-specific mRNAs.…”