The mechanism of infertility in flies and humans uncovered

Russian biologists have discovered that a small fragment of the gene responsible for the synthesis of Orb2 plays an important role in the fecundity of male fruit flies. If the "tail" of the gene is removed, three quarters of male Drosophila flies lose the ability to produce offspring. Since the fundamental mechanisms of germ cell formation in humans and insects are similar, the results will help explain the causes of infertility in males. A brief summary of the study is reported in a press release on the Russian Science Foundation's website.

It is known that genes of SREV family are responsible for maturation of germ cells in animals. In fruit flies, this family is represented by two genes: Orb and Orb2. Orb2 is involved in the proper development of male germ cells by regulating the activities of other proteins. Orb2 is also capable of autoregulation due to the presence of a special region, the 3'-untranslated region (3'NATO). The 3'NTO represents the "tail" of mRNA molecules from which the information for protein synthesis is read directly. Other proteins of SRV sit on this "tail" and regulate it.

Scientists used the CRISPR-Cas9 gene editing system to cut the 3'NATO from the Orb2 gene, making the corresponding mRNAs no longer able to bind to CREV proteins. About 75 percent of the insects were found to be infertile. Their development of spermatid precursor cells, spermatids, was impaired. When a spermatid matures, it develops the flagellum necessary for movement. However, in genetically altered cells, the flagellum was not formed correctly.

When a regulatory protein is attached to the 3'NATO, the mRNA is transported to a specific part of the cell. However, due to the lack of 3'NATO, the molecules did not get to the right region of the spermatid. According to the scientists, understanding this mechanism will help in the study of the role of CREVs in human spermatogenesis as well.


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