RT Journal Article
SR Electronic
T1 Translational specialization in pluripotency by RBPMS poises future lineage-decisions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.12.439420
DO 10.1101/2021.04.12.439420
A1 Deniz Bartsch
A1 Kaustubh Kalamkar
A1 Gaurav Ahuja
A1 Hisham Bazzi
A1 Argyris Papantonis
A1 Leo Kurian
YR 2021
UL http://biorxiv.org/content/early/2021/04/12/2021.04.12.439420.abstract
AB In mammals, translation is uniquely regulated at the exit of pluripotency to rapidly reprogram the proteome to enable lineage commitment. Yet, the developmental mediators of translational control and their mode-of-action remain elusive. Using human embryonic stem cells, we identified RBPMS as a vital translation specialization factor that allows selective translation of developmental regulators. RBPMS-driven translational control balances the abundance of cell-fate regulators to enable accurate lineage decisions upon receiving differentiation cues. RBPMS loss, without affecting pluripotency, specifically and severely impedes mesoderm specification and subsequent cardiogenesis. Mechanistically, the direct binding of RBPMS to 3’UTR allows selective translation of transcripts encoding developmental regulators including integral components of central morphogen signaling networks specifying mesoderm. RBPMS-loss results in aberrant retention of key translation initiation factors on ribosomal complexes. Our data unveil how emerging lineage choices from pluripotency are controlled by translational specialization via ribosomal platforms acting as a regulatory nexus for developmental cell fate decisions.IN BRIEF Future lineage choices from pluripotency are controlled by translational specialization. The RNA binding protein RBPMS is a vital translational specialization factor that unlocks the mesoderm commitment potential of pluripotent stem cells by enabling selective translation of cell-fate regulators instructing lineage decisions.HIGHLIGHTSLineage choices emerging from pluripotency are selectively controlled by translational specializationThe RNA-binding protein RBPMS is a translation specialization factor dedicated to mesoderm commitmentRBPMS-driven translational specialization enables accurate lineage commitment via balancing the availability of key morphogen signaling componentsRBPMS loss selectively impairs mesoderm commitment and subsequently impedes cardiogenesisRBPMS binds the 3’UTRs of target mRNAs to allow their selective translation; its depletion leads to aberrant retention of key translation initiation factors on ribosomal complexesCompeting Interest StatementThe authors have declared no competing interest.