Pozmanter Caitlin, Benner Leif, Kelly Sydney E, Curnutte Harrison, Emilfork Laura, Van Doren Mark
Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
Eunice Kennedy Shriver National Institute of Child Health and Development, National Institutes of Health, 6 Center Drive, Bldg. 6B Room 3B326, Bethesda, MD 20892, USA.
Genetics. 2025 Apr 17;229(4). doi: 10.1093/genetics/iyaf024.
Tudor domain-containing proteins are conserved across the animal kingdom for their function in germline development and fertility. Previously, we demonstrated that Tudor domain-containing protein 5-like plays an important role in the germline where it promotes male identity. However, Tudor domain-containing protein 5-like is also expressed in both the ovary and testis during later stages of germline development, suggesting that it plays a role in germline differentiation in both sexes. We found that Tudor domain-containing protein 5-like localizes to a potentially novel germline body and plays a role in posttranscriptional gene regulation. Additionally, embryos laid by Tdrd5l-mutant females exhibited reduced viability and displayed dorsal appendage defects suggesting a failure of proper dorsal-ventral patterning. As dorsal-ventral patterning is dependent on gurken (grk), we examined Gurken expression during oogenesis. We observed premature accumulation of Gurken protein in nurse cells indicating that translation is no longer properly repressed during mRNA transport to the oocyte. We also observed increased nurse cell accumulation of the cytoplasmic polyadenylation element binding protein Oo18 RNA-binding protein, a translational activator of grk. Decreasing orb function was able to partially rescue the Tdrd5l-mutant phenotype, and so defects in Orb expression are likely a primary cause of the defects in Tdrd5l mutants. Our data indicate that Tdrd5l is important for translational repression of maternal mRNAs such as orb, and possibly others, following their synthesis in the nurse cells and during their transport to the oocyte.
含Tudor结构域的蛋白质在动物界中因其在生殖系发育和生育能力方面的功能而保守。此前,我们证明含Tudor结构域的蛋白5样在生殖系中发挥重要作用,促进雄性特征。然而,含Tudor结构域的蛋白5样在生殖系发育后期的卵巢和睾丸中均有表达,这表明它在两性的生殖系分化中发挥作用。我们发现含Tudor结构域的蛋白5样定位于一个潜在的新型生殖系小体,并在转录后基因调控中发挥作用。此外,Tdrd5l突变雌性产下的胚胎活力降低,并表现出背附肢缺陷,提示背腹模式形成出现异常。由于背腹模式形成依赖于gurken(grk),我们在卵子发生过程中检测了Gurken的表达。我们观察到Gurken蛋白在滋养细胞中过早积累,这表明在mRNA向卵母细胞转运过程中,翻译不再受到适当抑制。我们还观察到细胞质聚腺苷酸化元件结合蛋白Oo18 RNA结合蛋白(grk的翻译激活因子)在滋养细胞中的积累增加。降低orb功能能够部分挽救Tdrd5l突变体表型,因此Orb表达缺陷可能是Tdrd5l突变体缺陷的主要原因。我们的数据表明,Tdrd5l对于母体mRNA(如orb以及可能的其他mRNA)在滋养细胞中合成后以及向卵母细胞转运过程中的翻译抑制很重要。