Eukaryotic translation initiation factor eIF4E-5 is required for spermiogenesis in Drosophila melanogaster

Abstract

Drosophila sperm development is characterized by extensive post-transcriptional regulation whereby thousands of transcripts are preserved for translation during later stages. A key step in translation initiation is the binding of eukaryotic initiation factor 4E (eIF4E) to the 5' mRNA cap. Drosophila has multiple paralogs of eIF4E, including four (eIF4E-3, -4, -5, and -7) that are highly expressed in the testis. Other than eIF4E-3, none of these has been characterized genetically. Here, using CRISPR/Cas9 mutagenesis, we determined that eIF4E-5 is essential for male fertility. eIF4E-5 mutants exhibit defects during post-meiotic stages, including a fully penetrant defect in individualization, resulting in failure to produce mature sperm. eIF4E-5 protein localizes to the distal ends of elongated spermatid cysts, where it regulates non-apoptotic caspase activity during individualization by promoting local accumulation of the E3 ubiquitin ligase inhibitor Soti. eIF4E-5 mutants also have mild defects in spermatid cyst polarization, similar to mutants affecting the cytoplasmic polyadenylation-element binding protein Orb2 and atypical protein kinase C (aPKC). Our results further extend the diversity of non-canonical eIF4Es that carry out distinct spatiotemporal roles during spermatogenesis.

Editing melon eIF4E associates with virus resistance and male sterility

“…Beyond their involvement in the canonical translation of cellular mRNAs, other biological functions have been demonstrated for eIFs. Animal and plant studies have shown that germ cell and embryonic fates are greatly affected by the eIF4 factor complexes unique to those cell types (Baker and Fuller, 2007; Callot and Gallois, 2014; Dinkova et al ., 2005; Friday and Keiper, 2015; Shao et al ., 2021). The use of genetics and biochemistry has also identified unique roles for eIF4E and eIF4G isoforms in reproduction.…”

“…The use of genetics and biochemistry has also identified unique roles for eIF4E and eIF4G isoforms in reproduction. Furthermore, eIF4Es in plants, flies and frogs have shown unique roles in sexual development, judging by the reproductive phenotypes resulting from their deficiencies (Callot and Gallois, 2014; Ghosh and Lasko, 2015; Mazier et al ., 2011; Patrick et al ., 2014; Shao et al ., 2021). Viruses could take advantage of these additional biological functions to control protein stability, regulate their replication and facilitate their intra‐ and intercellular movements.…”