RT Journal Article
SR Electronic
T1 Widespread translational remodeling during human neuronal differentiation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 156190
DO 10.1101/156190
A1 John D. Blair
A1 Dirk Hockemeyer
A1 Jennifer A. Doudna
A1 Helen S. Bateup
A1 Stephen N. Floor
YR 2017
UL http://biorxiv.org/content/early/2017/06/26/156190.abstract
AB Faithful cellular differentiation requires precise coordination of changes in gene expression. However, the relative contributions of transcriptional and translational regulation during human cellular differentiation are unclear. Here, we induced forebrain neuronal differentiation of human embryonic stem cells (hESCs) and characterized genomewide RNA and translation levels during neurogenesis. We find that thousands of genes change at the translation level across differentiation without a corresponding change in RNA level. Specifically, we identify mTOR complex 1 signaling as a key driver for elevated translation of translation-related genes in hESCs. In contrast, translational repression in active neurons is mediated by transcript 3′ UTRs, through regulatory sequences. Together, our findings identify a functional role for the dramatic 3′ UTR extensions that occur during brain development, and provide insights to interpret genetic variants in post-transcriptional control factors that influence neurodevelopmental disorders and diseases.