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Gag 蛋白 PEG10 与 RNA 结合，调节滋养层干细胞谱系特化。

The Gag protein PEG10 binds to RNA and regulates trophoblast stem cell lineage specification.

机构信息

Physiological Chemistry Department, Genentech, South San Francisco, California, United States of America.

Protein Chemistry Department, Genentech, South San Francisco, California, United States of America.

出版信息

PLoS One. 2019 Apr 5;14(4):e0214110. doi: 10.1371/journal.pone.0214110. eCollection 2019.

DOI:10.1371/journal.pone.0214110
PMID:30951545
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6450627/
Abstract

Peg10 (paternally expressed gene 10) is an imprinted gene that is essential for placental development. It is thought to derive from a Ty3-gyspy LTR (long terminal repeat) retrotransposon and retains Gag and Pol-like domains. Here we show that the Gag domain of PEG10 can promote vesicle budding similar to the HIV p24 Gag protein. Expressed in a subset of mouse endocrine organs in addition to the placenta, PEG10 was identified as a substrate of the deubiquitinating enzyme USP9X. Consistent with PEG10 having a critical role in placental development, PEG10-deficient trophoblast stem cells (TSCs) exhibited impaired differentiation into placental lineages. PEG10 expressed in wild-type, differentiating TSCs was bound to many cellular RNAs including Hbegf (Heparin-binding EGF-like growth factor), which is known to play an important role in placentation. Expression of Hbegf was reduced in PEG10-deficient TSCs suggesting that PEG10 might bind to and stabilize RNAs that are critical for normal placental development.

摘要

Peg10（父系表达基因 10）是一个印迹基因，对胎盘发育至关重要。它被认为来源于 Ty3-gyspy LTR（长末端重复）反转录转座子，并保留了 Gag 和 Pol 样结构域。在这里，我们展示 PEG10 的 Gag 结构域可以促进类似 HIV p24 Gag 蛋白的囊泡出芽。除了胎盘，PEG10 在一小部分小鼠内分泌器官中表达，并被鉴定为去泛素化酶 USP9X 的底物。与 PEG10 在胎盘发育中具有关键作用一致，PEG10 缺陷的滋养层干细胞（TSC）表现出向胎盘谱系分化的受损。在野生型、分化的 TSC 中表达的 PEG10 与许多细胞 RNA 结合，包括 Hbegf（肝素结合 EGF 样生长因子），已知其在胎盘形成中发挥重要作用。在 PEG10 缺陷的 TSC 中，Hbegf 的表达减少，表明 PEG10 可能与对正常胎盘发育至关重要的 RNA 结合并稳定这些 RNA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/8fb9ab516c98/pone.0214110.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/f23b2ebce616/pone.0214110.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/623a1f02fff4/pone.0214110.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/b4d89b0440b9/pone.0214110.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/f1b1a01629ae/pone.0214110.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/9eaa07035f0d/pone.0214110.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/2fbe9092a944/pone.0214110.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/8fb9ab516c98/pone.0214110.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/f23b2ebce616/pone.0214110.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/623a1f02fff4/pone.0214110.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/b4d89b0440b9/pone.0214110.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/f1b1a01629ae/pone.0214110.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/9eaa07035f0d/pone.0214110.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/2fbe9092a944/pone.0214110.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02af/6450627/8fb9ab516c98/pone.0214110.g007.jpg

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