Poster Presentation 6th Annual Meeting for Australasian Society for Stem Cell Research 2013

RELB forms a tri-partite complex with LIN28A and IMP3, co-localizes in stress granules, regulates expression of IGF2 and cell cycle genes, and arbitrates between proliferation and differentiation of human pluripotent stem cells. (#168)

Nilay Thakar 1 , Dmitry Ovchinnikov 1 , Marcus Hastie 2 , Jeffrey Gorman 2 , Ernst Wolvetang 1
  1. Stem Cell Engineering Group, Australian Institute for Bioengineering and Nanotechnology, St Lucia, Queensland, Australia
  2. Protein Discovery Centre, Queensland Institute of Medical Research, Herston, Queensland , Australia

The molecular mechanisms that orchestrate exit from pluripotency, cell cycle and lineage-specific differentiation in human pluripotent stem cells remain to be completely understood. RELB, a key non-canonical NFκB signaling pathway protein was previously implicated in controlling the switch between hESC proliferation and differentiation. Here we show that RELB maintains pluripotency of hESc and hIPSC via suppression of differentiation and enhances proliferation of these cells. We show RELB does this by a) forming a tri-partite complex with LIN28A and IMP3 (IGF-2 mRNA binding protein 3), b) that this interaction controls mRNA levels and protein expression of IGF-2 and key cell-cycle genes and c) that these proteins co-localize in stress granules in hESC and iPSC. Our data identify RELB as a novel regulator of human pluripotent stem cell proliferation and differentiation, and reveal a potential mechanism that involves RELB-mediated recruitment of IMP3 and LIN28 to cytosolic mRNA translation control domains.