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

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 indu

SUBMITTER: Tsanov KM 

PROVIDER: S-EPMC5182091 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature