The Francis Crick Institute, London, NW1 1AT, UK.
Imperial College of Science Technology and Medicine, London, W12 0BZ, UK.
Philos Trans R Soc Lond B Biol Sci. 2023 Nov 20;378(1890):20220242. doi: 10.1098/rstb.2022.0242. Epub 2023 Oct 2.
Peptidyl arginine deiminase 6 (PADI6) is a maternal factor that is vital for early embryonic development. Deletion and mutations of its encoding gene in female mice or women lead to early embryonic developmental arrest, female infertility, maternal imprinting defects and hyperproliferation of the trophoblast. PADI6 is the fifth and least well-characterized member of the peptidyl arginine deiminases (PADIs), which catalyse the post-translational conversion of arginine to citrulline. It is less conserved than the other PADIs, and currently has no reported catalytic activity. While there are many suggested functions of PADI6 in the early mouse embryo, including in embryonic genome activation, cytoplasmic lattice formation, maternal mRNA and ribosome regulation, and organelle distribution, the molecular mechanisms of its function remain unknown. In this review, we discuss what is known about the function of PADI6 and highlight key outstanding questions that must be answered if we are to understand the crucial role it plays in early embryo development and female fertility. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'.
肽基精氨酸脱亚氨酶 6（PADI6）是一种母源因子，对早期胚胎发育至关重要。在雌性小鼠或女性中，其编码基因的缺失和突变会导致早期胚胎发育停滞、女性不孕、母性印迹缺陷以及滋养层过度增殖。PADI6 是第五种也是研究最少的肽基精氨酸脱亚氨酶（PADIs）成员之一，它催化精氨酸到瓜氨酸的翻译后转化。它不如其他 PADIs 保守，目前没有报道的催化活性。虽然 PADI6 在早期小鼠胚胎中有许多被认为的功能，包括胚胎基因组激活、细胞质晶格形成、母体 mRNA 和核糖体调节以及细胞器分布，但它的功能的分子机制仍不清楚。在这篇综述中，我们讨论了 PADI6 的已知功能，并强调了如果要了解它在早期胚胎发育和女性生育力中所起的关键作用，必须回答的关键问题。本文是 Theo Murphy 会议议题“蛋白质瓜氨酸化的优缺点”的一部分。
