Gene regulation in Drosophila spermatogenesis clarified
A group of scientists at Osaka University has clarified, in experiments using Drosophila, a genus of fly that belongs to the family Drosophilidae, that Cyclophilin40 (Cyp40) regulates gene expression of generative cells in the testis by manipulating microRNA (miRNA), small RNA molecules necessary for spermatogenesis.
Cyp40 was known to assist the correct folding of unfolded proteins, but their physiological significance was unknown. This research group made Cyp40 knockout Drosophila and found that cyp40 mutants grew normally to adulthood but that the males exhibited infertility, meaning that Hsp90 co-chaperone Cyp40 plays essential roles for sperm maturation in flies.
The process of transforming genetic information encoded in DNA into proteins is called gene expression, which must be regulated to ensure that the correct cell differentiation is made.
For regulating gene expression, miRNA that causes RNA silencing is important. RNAs with less perfect sequence matches cause the RNA-induced silencing complex (RISC) to block the movement of the ribosomes on the mRNA so that the mRNA is not translated and does not produce a protein, thereby silencing that RNA. Small RNAs, such as microRNA (miRNA) or double-stranded small interfering RNA (siRNA), form RISCs to repress gene expression, with Argonaute (Ago) proteins serving as key players in RNA silencing.
In this study, since a loss of cyp40 function incurred changes in the accumulation of miRNAs, Cyp40 was found to directly regulate sRNA steady-state accumulation during RISC formation.
Their findings will lead to the confirmation that Cyp40 is essential for spermatogenesis in a wide range of animals and clarify causes of diseases such as azoospermia.
It is known that miRNAs regulate gene expression in plants. Since miRNAs are key regulators of gene expression in a variety of biological phenomena, it is necessary to study the possibility that Cyp40 plays a critical role in aspects other than spermatogenesis.
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The article, “Modulation of Ago2 Loading by Cyclophilin 40 Endows a Unique Repertoire of Functional miRNAs during Sperm Maturation in Drosophila,” was published in Cell Reports at DOI: https://doi.org/10.1016/j.celrep.2020.108380.
