RT Journal Article
SR Electronic
T1 Epiblast morphogenesis is controlled by selective mRNA decay triggered by LIN28A relocation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.15.433780
DO 10.1101/2021.03.15.433780
A1 Miha Modic
A1 Igor Ruiz de Los Mozos
A1 Sebastian Steinhauser
A1 Emiel van Genderen
A1 Silvia Schirge
A1 Valter Bergant
A1 Joel Ryan
A1 Christopher B Mulholland
A1 Rupert Faraway
A1 Flora C Y Lee
A1 Tajda Klobučar
A1 Juliane Merl-Pham
A1 Stephanie M Hauck
A1 Micha Drukker
A1 Sebastian Bultmann
A1 Heinrich Leonhardt
A1 Heiko Lickert
A1 Nicholas M Luscombe
A1 Derk ten Berge
A1 Jernej Ule
YR 2021
UL http://biorxiv.org/content/early/2021/03/16/2021.03.15.433780.abstract
AB The embryonic progression from naïve to primed pluripotency is accompanied by the rapid decay of pluripotency-associated mRNAs and a concomitant radical morphogenetic sequence of epiblast polarization, rosette formation and lumenogenesis. The mechanisms triggering and linking these events remain poorly understood. Guided by machine learning and metabolic RNA sequencing, we identified RNA binding proteins (RBPs), especially LIN28A, as primary mRNA decay factors. Using mRNA-RBP interactome capture, we revealed a dramatic increase in LIN28A mRNA binding during the naïve-rosette-primed pluripotency transition, driven by its nucleolar-to-cytoplasmic translocation. Cytoplasmic LIN28A binds to 3’UTRs of pluripotency-associated mRNAs to directly stimulate their decay and drive lumenogenesis. Accordingly, forced nuclear retention of LIN28A impeded lumenogenesis, impaired gastrulation, and caused an unforeseen embryonic multiplication. Selective mRNA decay, driven by nucleo-cytoplasmic RBP translocation, therefore acts as an intrinsic mechanism linking cell identity switches to the control of embryonic growth and morphogenesis.Competing Interest StatementThe authors have declared no competing interest.