MECP2 Is Post-transcriptionally Regulated during Human Neurodevelopment by Combinatorial Action of RNA-Binding Proteins and miRNAs

• DOI: 10.1016/j.celrep.2016.09.049
• Publication Date: 2016-10-11T16:00:27Z
• Authors: Deivid C. Rodrigues; Dae-Sung Kim; Guang Yang; Kirill Zaslavsky; Kevin C.H. Ha; Rebecca S.F. Mok; P. Joel Ross; Melody Zhao; Alina Piekna; Wei Wei; Benjamin J. Blencowe; Quaid Morris; James Ellis
• Keywords: MeCP2; Translational regulation

A progressive increase in MECP2 protein levels is a crucial and precisely regulated event during neurodevelopment, but the underlying mechanism unclear. We report that post-transcriptionally vitro differentiation of human embryonic stem cells (hESCs) into cortical neurons. Using reporters to identify functional RNA sequences 3′ UTR genetic manipulations explore role interacting factors on endogenous MECP2, we discover combinatorial mechanisms regulate stability translation. The RNA-binding PUM1 pluripotent-specific microRNAs destabilize long hESCs. Hence, appears lengthen as isoform becomes stable Meanwhile, translation repressed by TIA1 hESCs until HuC predominates neurons, resulting switch translational enhancement. Ultimately, UTR-directed fine-tuning differentially modulates two cell types appropriate for normal neurodevelopment.