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Leesch, K. F.

Publications and source records attributed to Leesch, K. F..

2 recordsLinked to original sources

A molecular network of conserved factors keeps ribosomes dormant in the egg

Ribosomes are produced in large quantities during oogenesis and stored in the egg. However, the egg and early embryo are translationally repressed. Using mass-spectrometry and cryo-EM analyses of ribosomes isolated from zebrafish and Xenopus eggs and embryos, we provide molecular evidence that ribosomes transition from a dormant to an active state during the first hours of embryogenesis. Dormant ribosomes are associated with four conserved factors that form two modules and occupy functionally important sites of the ribosome: a Habp4-eEF2 module that stabilizes ribosome levels and a Dap1b/Dapl1-eIF5a module that represses translation. Dap1b/Dapl1 is a newly discovered translational inhibitor that stably inserts into the polypeptide exit tunnel. Thus, a developmentally programmed, conserved ribosome state plays a key role in ribosome storage and translational repression in the egg.

biochemistry↗

NMD is required for timely cell fate transitions by fine-tuning gene expression and controlling translation

Cell fate transitions depend on balanced rewiring of transcription and translation programmes to mediate ordered developmental progression. Here we identify a feedback loop between nonsense-mediated mRNA decay (NMD) and translation initiation. We show that NMD controls the translation initiation factor Eif4a2 and its premature termination codon encoding isoform (Eif4a2PTC). NMD deficiency leads to translation of a specific truncated Eif4a2 protein, which elicits increased translation rates and is causative for significant delays in mouse embryonic stem cell (ESC) differentiation. Our results show identical mRNA targets for Smg5, Smg6 and Smg7, but illustrate a clear hierarchy between KOs in amplitude of target deregulation and differentiation phenotype (Smg5 > Smg6 > Smg7). This hierarchy highlights heterodimer independent functions for Smg5 and Smg7. Together, our findings expose an intricate link between mRNA stability and translation initiation control, that must be maintained for normal dynamics of cell state transitions.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cell biology↗