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Translational Control during Developmental Transitions - PubMed

  • ️Tue Jan 01 2019

Review

Translational Control during Developmental Transitions

Felipe Karam Teixeira et al. Cold Spring Harb Perspect Biol. 2019.

Abstract

The many steps of gene expression, from the transcription of a gene to the production of its protein product, are well understood. Yet, transcriptional regulation has been the focal point for the study of gene expression during development. However, quantitative studies reveal that messenger RNA (mRNA) levels are not necessarily good predictors of the respective proteins' levels in a cell. This discrepancy is, at least in part, the result of developmentally regulated, translational mechanisms that control the spatiotemporal regulation of gene expression. In this review, we focus on translational regulatory mechanisms mediating global transitions in gene expression: the shift from the maternal to the embryonic developmental program in the early embryo and the switch from the self-renewal of stem cells to differentiation in the adult.

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Figures

Figure 1.
Figure 1.

Mechanisms of translational control during embryo development. Examples of modules regulating protein synthesis during the first steps of embryo development, a period during which the zygotic genome is mostly transcriptionally quiescent. (A) Maternal-to-zygotic transition (MZT). (Left) Fertilized Drosophila (top), Xenopus (bottom), and zebrafish (right) embryos are transcriptionally silent and contain maternally synthesized gene products that sustain development and lay down the basic structures and embryonic axes. (Right) During the MZT, maternal products are largely degraded, and zygotic transcription ensues. This allows asynchrony in cell divisions and morphogenetic cell movements of gastrulation needed for body plan building. (B) Messenger RNA (mRNA) localization is mediated by RNA-binding proteins that recognize secondary structures present in the 3′ untranslated region (UTR) of target mRNAs. Assembled adaptor ribonucleoprotein complexes (RNPs) are recruited to molecular motors and delivered to specific intracellular domains. (C) Translational repression can be actively established on targets by RNA-binding proteins—such as Bruno (Bru) and Smaug (Smg)—that recognize sequences within the transcript 3′UTRs and recruit other factors to block translation initiation. (D) Translational activation is associated with the recruitment and activity of poly(A) [p(A)] polymerases and interactions between the poly(A)-binding protein and translation eukaryotic initiation factor (eIF)4G and eIF4E on target mRNA transcripts. (E) Base complementarity-targeted microRNA regulation is mediated by the RNA-induced silencing complex (RISC) and induces large-scale translational repression and CCR4/NOT-dependent target mRNA decay during the MZT. (F) Local protection of evenly distributed mRNAs against bulk degradation, which is mediated by localized RNA-binding proteins recognizing specific motifs in the 3′UTR of target mRNAs leads to spatially regulated expression at the subcellular level. (G) Slower ribosome translocation rates over transcripts containing suboptimal codons trigger mRNA deadenylation and decay during embryo development. rRNA, ribosomal RNA; miRNA, microRNA.

Figure 2.
Figure 2.

Translational control during stem cell maintenance and differentiation. Actively dividing stem cells (left) present lower global protein synthesis rates (fewer ribosomes attached to messenger RNAs [mRNAs]) in comparison to their immediate differentiating daughters (right). Yet, ribosomal RNA synthesis and ribosome biogenesis (shown by a black factory) are up-regulated compared with their differentiated progeny. This has been observed in several stem cells, such as Drosophila adult female germline and mouse embryonic stem cells, indicating that ribosome biogenesis and protein synthesis rates may be uncoupled in such stem cell systems.

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