title: The RNA binding protein ESRP1 fine-tunes the expression of pluripotency-related factors in mouse embryonic stem cells.
abstract: In pluripotent stem cells, there is increasing evidence for crosstalk between post-transcriptional and transcriptional networks, offering multifold steps at which pluripotency can be controlled. In addition to well-studied transcription factors, chromatin modifiers and miRNAs, RNA-binding proteins are emerging as fundamental players in pluripotency regulation. Here, we report a new role for the RNA-binding protein ESRP1 in the control of pluripotency. Knockdown of Esrp1 in mouse embryonic stem cells induces, other than the well-documented epithelial to mesenchymal-like state, also an increase in expression of the core transcription factors Oct4, Nanog and Sox2, thereby enhancing self-renewal of these cells. Esrp1-depleted embryonic stem cells displayed impaired early differentiation in vitro and formed larger teratomas in vivo when compared to control embryonic stem cells. We also show that ESRP1 binds to Oct4 and Sox2 mRNAs and decreases their polysomal loading. ESRP1 thus acts as a physiological regulator of the finely-tuned balance between self-renewal and commitment to a restricted developmental fate. Importantly, both mouse and human epithelial stem cells highly express ESRP1, pinpointing the importance of this RNA-binding protein in stem cell biology.
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Turin, Italy.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Fagoonee
authors.forename: Claudia
authors.initials: C
authors.lastname: Bearzi
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Di Cunto
authors.forename: John G
authors.initials: JG
authors.lastname: Clohessy
authors.forename: Roberto
authors.initials: R
authors.lastname: Rizzi
authors.forename: Markus
authors.initials: M
authors.lastname: Reschke
authors.forename: Emanuela
authors.initials: E
authors.lastname: Tolosano
authors.forename: Paolo
authors.initials: P
authors.lastname: Provero
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pandolfi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Silengo
authors.forename: Fiorella
authors.initials: F
authors.lastname: Altruda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000588453:ESRP1 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins