The Gag protein PEG10 binds to RNA and regulates trophoblast stem cell lineage specification.
oleh: Mona Abed, Erik Verschueren, Hanna Budayeva, Peter Liu, Donald S Kirkpatrick, Rohit Reja, Sarah K Kummerfeld, Joshua D Webster, Sarah Gierke, Mike Reichelt, Keith R Anderson, Robert J Newman, Merone Roose-Girma, Zora Modrusan, Hazal Pektas, Emin Maltepe, Kim Newton, Vishva M Dixit
| Format: | Article |
|---|---|
| Diterbitkan: | Public Library of Science (PLoS) 2019-01-01 |
Deskripsi
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.