LIN28 phosphorylation by MAPK/ERK couples signalling to the post-transcriptional control of pluripotency.
Nat Cell Biol
; 19(1): 60-67, 2017 Jan.
Article
en En
| MEDLINE
| ID: mdl-27992407
ABSTRACT
Signalling and post-transcriptional gene control are both critical for the regulation of pluripotency, yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein, has emerged as a central post-transcriptional regulator of cell fate through blockade of let-7 microRNA biogenesis and direct modulation of mRNA translation. Here we show that LIN28 is phosphorylated by MAPK/ERK in pluripotent stem cells, which increases its levels via post-translational stabilization. LIN28 phosphorylation had little impact on let-7 but enhanced the effect of LIN28 on its direct mRNA targets, revealing a mechanism that uncouples LIN28's let-7-dependent and -independent activities. We have linked this mechanism to the induction of pluripotency by somatic cell reprogramming and the transition from naive to primed pluripotency. Collectively, our findings indicate that MAPK/ERK directly impacts LIN28, defining an axis that connects signalling, post-transcriptional gene control, and cell fate regulation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transcripción Genética
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Proteínas de Unión al ARN
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Sistema de Señalización de MAP Quinasas
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Células Madre Pluripotentes
Límite:
Animals
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Humans
Idioma:
En
Revista:
Nat Cell Biol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos