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Unconventional Translation Initiation Factor EIF2A is required for Drosophila spermatogenesis

David D. Lowe, Denise J. Montell
doi: https://doi.org/10.1101/2021.03.28.437419
David D. Lowe
aDepartment of Molecular Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, California 93106
bDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115
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Denise J. Montell
aDepartment of Molecular Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, California 93106
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  • For correspondence: dmontell@ucsb.edu
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Abstract

The eukaryotic initiation factor EIF2A is an unconventional translation factor required for initiation of protein synthesis from non-AUG codons from a variety of transcripts, including oncogenes and stress related genes in mammalian cells. Its function in multicellular organisms has not been reported. Here, we identify and characterize mutant alleles of the CG7414 gene, which encodes the Drosophila EIF2A ortholog. We identified that CG7414 undergoes sex-specific splicing that regulates its male-specific expression. We characterized a Mi{Mic} transposon insertion that disrupts the coding regions of all predicted isoforms and is a genetic null allele, and a PBac transposon insertion into an intron, which is a hypomorph. The Mi{Mic} allele is homozygous lethal, while the viable progeny from the hypomorphic PiggyBac allele are male sterile and female fertile. In dEIF2A mutant flies, sperm failed to individualize due to defects in F-actin cones and failure to form and maintain cystic bulges, ultimately leading to sterility. These results demonstrate that EIF2A is essential in a multicellular organism, both for normal development and spermatogenesis, and provide an entree into the elucidation of the role of EIF2A and unconventional translation in vivo.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted March 29, 2021.
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Unconventional Translation Initiation Factor EIF2A is required for Drosophila spermatogenesis
David D. Lowe, Denise J. Montell
bioRxiv 2021.03.28.437419; doi: https://doi.org/10.1101/2021.03.28.437419
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Unconventional Translation Initiation Factor EIF2A is required for Drosophila spermatogenesis
David D. Lowe, Denise J. Montell
bioRxiv 2021.03.28.437419; doi: https://doi.org/10.1101/2021.03.28.437419

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