Post-transcriptional regulation of development

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Production of fertile sperm requires expression of more than 1000 proteins that are needed at different stages of sperm development. For example, some proteins act early in sperm development to ensure the sperm contains the correct number of chromosomes. Other proteins act later in sperm development to form the whip-like tail that propels the sperm towards the egg during fertilization. Despite recent progress in understanding how sperm cells develop, little is known about how proteins are made at the right place and time to form fertile sperm. We recently discovered that a factor called eIF4E-3 controls protein synthesis during sperm development in fruit flies. eIF4E-3 is a member of a conserved family of proteins that regulates initiation of protein synthesis. In the absence of eIF4E-3, some sperm proteins are expressed at lower than normal levels, interfering with cell division and sperm development and causing male sterility. Unexpectedly, knockdown of the canonical eIF4E (eIF4E-1 in flies) resembles loss of eIF4E-3, suggesting eIF4E-3 and eIF4E-1 may regulate similar proteins. However, eIF4E-3 is missing important amino acids, suggesting it may be regulated differently from eIF4E-1. In addition, fruit flies make three other testis-specific eIF4E proteins, eIF4E-4, -5 and -7. The proposed experiments will use a combination of cell biology, genetics, molecular biology and biochemistry to discover the role and regulation of eIF4E-3, determine the roles of the other eIF4Es, and identify target genes regulated by these eIF4Es during sperm development.