The Gag Protein PEG10 Binds to RNA and Regulates Trophoblast Stem Cell Lineage Specification.

Mona Abed; Erik Verschueren; Hanna G. Budayeva; Peter Jianrui Liu; Donald S. Kirkpatrick; Rohit Reja; Sarah Kummerfeld; Joshua D. Webster; Sarah Gierke; Mike Reichelt; Keith R. Anderson; Robert J. Newman; Merone Roose‐Girma; Zora D. Modrusan; Hazal Pektas; Emin Maltepe; Kim Newton; Vishva M. Dixit

doi:10.1371/journal.pone.0214110

Molecular BiologyPLoS ONEApr 5, 2019

Peer-reviewed journal article

The Gag Protein PEG10 Binds to RNA and Regulates Trophoblast Stem Cell Lineage Specification.

Mona Abed, Erik Verschueren iD, Hanna G. Budayeva iD, Peter Jianrui Liu iD, Donald S. Kirkpatrick iD, Rohit Reja iD, Sarah Kummerfeld iD, Joshua D. Webster iD, Sarah Gierke iD, Mike Reichelt iD, Keith R. Anderson iD, Robert J. Newman iD, Merone Roose‐Girma iD, Zora D. Modrusan iD, Hazal Pektas, Emin Maltepe iD, Kim Newton iD, Vishva M. Dixit iD

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.

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