title: The THO complex regulates pluripotency gene mRNA export and controls embryonic stem cell self-renewal and somatic cell reprogramming.
abstract: Embryonic stem cell (ESC) self-renewal and differentiation are governed by a broad-ranging regulatory network. Although the transcriptional regulatory mechanisms involved have been investigated extensively, posttranscriptional regulation is still poorly understood. Here we describe a critical role of the THO complex in ESC self-renewal and differentiation. We show that THO preferentially interacts with pluripotency gene transcripts through Thoc5 and is required for self-renewal at least in part by regulating their export and expression. During differentiation, THO loses its interaction with those transcripts due to reduced Thoc5 expression, leading to decreased expression of pluripotency proteins that facilitates exit from self-renewal. THO is also important for the establishment of pluripotency, because its depletion inhibits somatic cell reprogramming and blastocyst development. Together, our data indicate that THO regulates pluripotency gene mRNA export to control ESC self-renewal and differentiation, and therefore uncover a role for this aspect of posttranscriptional regulation in stem cell fate specification.
authors: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors: Li
authors: L
authors: Wang
authors: Yi-Liang
authors: YL
authors: Miao
authors: Xiaofeng
authors: X
authors: Zheng
authors: Brad
authors: B
authors: Lackford
authors: Bingying
authors: B
authors: Zhou
authors: Leng
authors: L
authors: Han
authors: Chengguo
authors: C
authors: Yao
authors: James M
authors: JM
authors: Ward
authors: Adam
authors: A
authors: Burkholder
authors: Inna
authors: I
authors: Lipchina
authors: David C
authors: DC
authors: Fargo
authors: Konrad
authors: K
authors: Hochedlinger
authors: Yongsheng
authors: Y
authors: Shi
authors: Carmen J
authors: CJ
authors: Williams
authors: Guang
authors: G
authors: Hu
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D065150:Cellular Reprogramming / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D034443:RNA Transport / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D012333:RNA, Messenger