LIN28 phosphorylation by MAPK/ERK couples signalling to the post-transcriptional control of pluripotency

Nat Cell Biol. 2017 Jan;19(1):60-67. doi: 10.1038/ncb3453. Epub 2016 Dec 19.


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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • MAP Kinase Signaling System*
  • Mass Spectrometry
  • Mice
  • Mice, Transgenic
  • MicroRNAs / metabolism
  • Mouse Embryonic Stem Cells / metabolism
  • Phosphorylation
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism*
  • Protein Domains
  • Protein Stability
  • RNA-Binding Proteins / metabolism*
  • Transcription, Genetic*


  • Lin-28 protein, mouse
  • MicroRNAs
  • RNA-Binding Proteins
  • mirnlet7 microRNA, mouse