Multiple mechanisms collaborate to repress nanos translation in the Drosophila ovary and embryo
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA. RNA
(Impact Factor: 4.94).
04/2011; 17(5):967-77. DOI: 10.1261/rna.2478611
Translational control of gene expression is essential for development in organisms that rely on maternal mRNAs. In Drosophila, translation of maternal nanos (nos) mRNA must be restricted to the posterior of the early embryo for proper patterning of the anterior-posterior axis. Spatial control of nos translation is coordinated through the localization of a small subset of nos mRNA to the posterior pole late in oogenesis, activation of this localized mRNA, and repression of the remaining unlocalized nos mRNA throughout the bulk cytoplasm. Translational repression is mediated by the interaction of a cis-acting element in the nos 3' untranslated region with two proteins, Glorund (Glo) and Smaug (Smg), that function in the oocyte and embryo, respectively. The mechanism of Glo-dependent repression is unknown. Previous work suggests that Smg represses translation initiation but this model is not easily reconciled with evidence for polysome association of repressed nos mRNA. Using an in vitro translation system, we have decoupled translational repression of nos imposed during oogenesis from repression during embryogenesis. Our results suggest that both Glo and Smg regulate translation initiation, but by different mechanisms. Furthermore, we show that, during late oogenesis, nos translation is also repressed post-initiation and provide evidence that Glo mediates this event. This post-initiation block is maintained into embryogenesis during the transition to Smg-dependent regulation. We propose that the use of multiple modes of repression ensures inactivation of nos RNA that is translated at earlier stages of oogenesis and maintenance of this inactivate state throughout late oogenesis into embryogenesis.
Available from: Nathalie Oulhen
- "RNAs rather than transcribe them de novo, consistent with the broad distribution of RNAs encoding Vasa and Seawi in early embryos that is later refined to the sMics during gastrulation (Juliano et al., 2006; Voronina et al., 2008). In other organisms such as Drosophila, mRNA localization is an important mechanism during early development (Becalska and Gavis, 2009) and localization of nanos RNA in the germ line depends on sites in its 3'-UTR (Andrews et al., 2011; Gavis et al., 1996). "
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ABSTRACT: The formation of the germ line in an embryo marks a fresh round of reproductive potential. The developmental stage and location within the embryo where the primordial germ cells (PGCs) form, however, differs markedly among species. In many animals, the germ line is formed by an inherited mechanism, in which molecules made and selectively partitioned within the oocyte drive the early development of cells that acquire this material to a germ-line fate. In contrast, the germ line of other animals is fated by an inductive mechanism that involves signaling between cells that directs this specialized fate. In this review, we explore the mechanisms of germ-line determination in echinoderms, an early-branching sister group to the chordates. One member of the phylum, sea urchins, appears to use an inherited mechanism of germ-line formation, whereas their relatives, the sea stars, appear to use an inductive mechanism. We first integrate the experimental results currently available for germ-line determination in the sea urchin, for which considerable new information is available, and then broaden the investigation to the lesser-known mechanisms in sea stars and other echinoderms. Even with this limited insight, it appears as sea stars, and perhaps the majority of the echinoderm taxon, rely on inductive mechanisms for germ-line fate determination. This enables a strongly contrasted picture for germ-line determination in this phylum, but one for which transitions between different modes of germ-line determination might now be experimentally addressed. Mol. Reprod. Dev. © 2013 Wiley Periodicals, Inc.
Molecular Reproduction and Development 07/2014; 81(8). DOI:10.1002/mrd.22223 · 2.53 Impact Factor
Available from: Sandi Clement
- "Alternatively, the dramatic increase in TTP levels that occurs during LPS stimulation could render the cellular levels of hnRNP F limiting for the interaction. The remodeling of mRNPs that takes place to allow mRNA degradation is generally associated with repression of translation initiation  and hnRNP F has previously been implicated in translational repression , , ; thus, an important question for future study is whether this activity of hnRNP F plays a role in TTP/BRF-mediated degradation of ARE-mRNAs. "
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ABSTRACT: The tristetraprolin (TTP) family of zinc-finger proteins, TTP, BRF1 and BRF2, regulate the stability of a subset of mRNAs containing 3'UTR AU-rich elements (AREs), including mRNAs coding for cytokines, transcription factors, and proto-oncogenes. To better understand the mechanism by which TTP-family proteins control mRNA stability in mammalian cells, we aimed to identify TTP- and BRF1-interacting proteins as potential TTP-family co-factors. This revealed hnRNP F as a prominent interactor of TTP and BRF1. While TTP, BRF1 and hnRNP F are all RNA binding proteins (RBPs), the interaction of hnRNP F with TTP and BRF1 is independent of RNA. Depletion of hnRNP F impairs the decay of a subset of TTP-substrate ARE-mRNAs by a mechanism independent of the extent of hnRNP F binding to the mRNA. Taken together, these findings implicate hnRNP F as a co-factor in a subset of TTP/BRF-mediated mRNA decay and highlight the importance of RBP cooperativity in mRNA regulation.
PLoS ONE 06/2014; 9(6):e100992. DOI:10.1371/journal.pone.0100992 · 3.23 Impact Factor
Available from: Thomas Preiss
- "On the other hand, repression in late oocytes is poly(A) dependent, which may reflect an effect of Glorund on initiation as well. A comparison of the polysomal association of nos mRNA in total ovary extracts, which are enriched for early-stage oocytes, with that in late ovary and embryo extracts indicates a gradual shift to lighter fractions, consistent with the temporal acquisition of distinct mechanisms of translational repression (Andrews et al. 2011). "
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ABSTRACT: Messenger RNAs (mRNAs), the templates for translation, have evolved to harbor abundant cis-acting sequences that affect their posttranscriptional fates. These elements are frequently located in the untranslated regions and serve as binding sites for trans-acting factors, RNA-binding proteins, and/or small non-coding RNAs. This article provides a systematic synopsis of cis-acting elements, trans-acting factors, and the mechanisms by which they affect translation. It also highlights recent technical advances that have ushered in the era of transcriptome-wide studies of the ribonucleoprotein complexes formed by mRNAs and their trans-acting factors.
Cold Spring Harbor perspectives in biology 07/2012; 4(7):a012245. DOI:10.1101/cshperspect.a012245 · 8.68 Impact Factor
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