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PMID:24315442

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Citation

Wang, L, Miao, YL, Zheng, X, Lackford, B, Zhou, B, Han, L, Yao, C, Ward, JM, Burkholder, A, Lipchina, I, Fargo, DC, Hochedlinger, K, Shi, Y, Williams, CJ and Hu, G (2013) The THO complex regulates pluripotency gene mRNA export and controls embryonic stem cell self-renewal and somatic cell reprogramming. Cell Stem Cell 13:676-90

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.

Links

PubMed PMC3962795 Online version:10.1016/j.stem.2013.10.008

Keywords

Animals; Blastocyst/cytology; Blastocyst/metabolism; Cell Differentiation/genetics; Cell Line; Cell Proliferation; Cellular Reprogramming/genetics; Embryonic Stem Cells/cytology; Embryonic Stem Cells/metabolism; Mice; Models, Biological; Multiprotein Complexes/metabolism; Pluripotent Stem Cells/metabolism; Protein Binding/genetics; RNA Transport/genetics; RNA, Messenger/genetics; RNA, Messenger/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:THOC2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q5U4D9
PR:Q7TMY4
PR:Q8BKT7
PR:Q8R3N6
PR:Q8VE80

F

Seeded From UniProt

complete

MOUSE:THOC2

acts_upstream_of_or_within

GO:0017145: stem cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:THOC2

acts_upstream_of_or_within

GO:0001824: blastocyst development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:THOC2

acts_upstream_of_or_within

GO:0000902: cell morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:THOC2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:THOC2

acts_upstream_of_or_within

GO:0010793: regulation of mRNA export from nucleus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:THOC2

acts_upstream_of_or_within

GO:0010468: regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:THOC2

enables

GO:0003729: mRNA binding

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:PO5F1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CDX2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:THOC6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:B1AZI6

F

Seeded From UniProt

complete

MOUSE:THOC7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:B1AZI6

F

Seeded From UniProt

complete

MOUSE:THOC5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:B1AZI6

F

Seeded From UniProt

complete

MOUSE:THOC5

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:THOC1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:B1AZI6

F

Seeded From UniProt

complete

MOUSE:THOC3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:B1AZI6

F

Seeded From UniProt

complete

MOUSE:PO5F1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:THOC5

acts_upstream_of_or_within

GO:0017145: stem cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:THOC5

acts_upstream_of_or_within

GO:0010793: regulation of mRNA export from nucleus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:THOC5

acts_upstream_of_or_within

GO:0010468: regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:THOC5

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:THOC5

enables

GO:0003729: mRNA binding

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:THOC5

acts_upstream_of_or_within

GO:0001824: blastocyst development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:THOC5

acts_upstream_of_or_within

GO:0000902: cell morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:THOC5

acts_upstream_of_or_within

GO:2000035: regulation of stem cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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