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

被引:51
作者
Abed, Mona [1 ]
Verschueren, Erik [2 ]
Budayeva, Hanna [2 ]
Liu, Peter [2 ]
Kirkpatrick, Donald S. [2 ]
Reja, Rohit [3 ]
Kummerfeld, Sarah K. [3 ,7 ]
Webster, Joshua D. [4 ]
Gierke, Sarah [4 ]
Reichelt, Mike [4 ]
Anderson, Keith R. [5 ]
Newman, Robert J. [5 ]
Roose-Girma, Merone [5 ]
Modrusan, Zora [5 ]
Pektas, Hazal [6 ]
Maltepe, Emin [6 ]
Newton, Kim [1 ]
Dixit, Vishva M. [1 ]
机构
[1] Genentech Inc, Physiol Chem Dept, San Francisco, CA 94080 USA
[2] Genentech Inc, Prot Chem Dept, San Francisco, CA USA
[3] Genentech Inc, Bioinformat & Computat Biol Dept, San Francisco, CA USA
[4] Genentech Inc, Pathol Dept, San Francisco, CA USA
[5] Genentech Inc, Mol Biol Dept, San Francisco, CA USA
[6] Univ Calif San Francisco, Div Neonatol, Ctr Reprod Sci, San Francisco, CA 94143 USA
[7] Garvin Inst Med Res, Kinghorn Ctr Clin Genom, Darlinghurst, NSW, Australia
关键词
TRANSPOSABLE ELEMENTS; PACKAGING SIGNAL; GENOME; GENE; USP9X; RETROTRANSPOSON; UBIQUITINATION; EXPRESSION; STABILITY; ENVELOPE;
D O I
10.1371/journal.pone.0214110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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页数:18
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