PLoS ONE (Jan 2019)

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

  • 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

DOI
https://doi.org/10.1371/journal.pone.0214110
Journal volume & issue
Vol. 14, no. 4
p. e0214110

Abstract

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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.