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

Nature Cell Biology 19, 60 (2017). doi:10.1038/ncb3453 Authors: Kaloyan M. Tsanov, Daniel S. Pearson, Zhaoting Wu, Areum Han, Robinson Triboulet, Marc T. Seligson, John T. Powers, Jihan K. Osborne, Susan Kane, Steven P. Gygi, Richard I. Gregory & George Q. Daley 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.
Source: Nature Cell Biology - Category: Cytology Authors: Tags: Letter Source Type: research