mRNA poly(A)-tail changes specified by deadenylation broadly reshape translation in Drosophila oocytes and early embryos

Eichhorn, Stephen W.; Subtelny, Alexander O.; Kronja, Iva; Kwasnieski, Jamie C.; Orr‐Weaver, Terry L.; Bartel, David P.

doi:10.7554/elife.16955

Cited by 154 publications

(238 citation statements)

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“…3 ′ UTRs are common targets of RBPs and miRNAs that regulate mRNA stability and translation (Matoulkova et al 2012). In transcriptionally silent embryos, maternal mRNA translation is tightly controlled by regulation of poly(A) tail length, whereas mRNA stabilities remain largely unaffected (Subtelny et al 2014;Eichhorn et al 2016). Analysis of available ribosome and poly(A) tail profiling data (Lee et al 2013;Subtelny et al 2014) revealed that Hnrnpa1 targets harbor significantly longer poly(A) tails (median length: 34.4 and 28.1, P = 7 × 10 −60 ) and display higher TE than nonbound mRNA counterparts (median TE: 0.94 and 0.53, P = 5.02 × 10…”

Section: Resultsmentioning

confidence: 99%

“…Third, we show that the mutation of the AGGGA hexanucleotide Hnrnpa1 binding motif in the 3 ′ UTR of an Hnrnpa1 target decreases Hnrnpa1 binding, shortens the poly(A) tail, and decreases translational output of a eGFP reporter. It has been proposed that selective deadenylation of maternal mRNAs is likely a major determinant of the differences in poly(A) tail length and TE between maternal transcripts in fly embryos, whereas CPE-mediated cytoplasmic polyadenylation creates these differences in vertebrates (Eichhorn et al 2016). Thus, Hnrnpa1 likely protects transcripts from active deadenylation or promotes their polyadenylation in zebrafish.…”

Section: Discussionmentioning

confidence: 99%

“…This switch in developmental control from maternal to zygotic instructions is known as maternal-to-zygotic transition (MZT). Recent studies have provided insight into embryonic transcriptomes during MZT, identifying the earliest zygotic transcripts and revealing dynamic, highly orchestrated changes in maternal mRNA stability and translation that are important for establishment of ZGA (Thomsen et al 2010;Aanes et al 2011;Pauli et al 2012;Harvey et al 2013;Lee et al 2013;Paranjpe et al 2013;Heyn et al 2014;Subtelny et al 2014;Eichhorn et al 2016;Lim et al 2016).…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

“…Cytoplasmic polyadenylation represents a conserved mechanism for translational enhancement of dormant mRNAs with short poly(A) tails (Bettegowda and Smith 2007). Strong coupling between poly(A) tail length and translation efficiency (TE) has been observed in the cleavage embryos of many species (Subtelny et al 2014;Eichhorn et al 2016;Lim et al 2016), although the molecular mechanisms that enable this coupling remain unclear. Recent studies have begun to determine a variety of mechanisms through which maternal mRNA clearance is accomplished (Giraldez et al 2006;Tadros et al 2007;Lund et al 2009;Tadros and Lipshitz 2009;Barckmann et al 2015;Bazzini et al 2016;Mishima and Tomari 2016).…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

“…Since maternal mRNAs do not change their expression levels between preZGA and ZGA, as evidenced by our RT-qPCR analysis (Supplemental Fig. S4F) and several previous studies (Voeltz and Steitz 1998;Subtelny et al 2014;Eichhorn et al 2016;Mishima and Tomari 2016), we utilized the absolute number of iCLIP tags as a measure of the Hnrnpa1 binding to individual mRNAs. Surprisingly, a comparison of iCLIP tag numbers revealed a >1.5-fold decrease in Hnrnpa1 association with 70% of mRNAs at the ZGA stage (Fig.…”

Section: Rna-protein Interactions In Zebrafish Embryosmentioning

confidence: 99%

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Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition

Despic

Dejung

et al. 2017

Genome Res.

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During the maternal-to-zygotic transition (MZT), transcriptionally silent embryos rely on post-transcriptional regulation of maternal mRNAs until zygotic genome activation (ZGA). RNA-binding proteins (RBPs) are important regulators of posttranscriptional RNA processing events, yet their identities and functions during developmental transitions in vertebrates remain largely unexplored. Using mRNA interactome capture, we identified 227 RBPs in zebrafish embryos before and during ZGA, hereby named the zebrafish MZT mRNA-bound proteome. This protein constellation consists of many conserved RBPs, some of which are potential stage-specific mRNA interactors that likely reflect the dynamics of RNA-protein interactions during MZT. The enrichment of numerous splicing factors like hnRNP proteins before ZGA was surprising, because maternal mRNAs were found to be fully spliced. To address potentially unique roles of these RBPs in embryogenesis, we focused on Hnrnpa1. iCLIP and subsequent mRNA reporter assays revealed a function for Hnrnpa1 in the regulation of poly(A) tail length and translation of maternal mRNAs through sequence-specific association with 3 ′ UTRs before ZGA. Comparison of iCLIP data from two developmental stages revealed that Hnrnpa1 dissociates from maternal mRNAs at ZGA and instead regulates the nuclear processing of pri-mir-430 transcripts, which we validated experimentally. The shift from cytoplasmic to nuclear RNA targets was accompanied by a dramatic translocation of Hnrnpa1 and other pre-mRNA splicing factors to the nucleus in a transcription-dependent manner. Thus, our study identifies global changes in RNAprotein interactions during vertebrate MZT and shows that Hnrnpa1 RNA-binding activities are spatially and temporally coordinated to regulate RNA metabolism during early development.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

Section: Rna-protein Interactions In Zebrafish Embryosmentioning

confidence: 99%

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Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition

Despic

Dejung

et al. 2017

Genome Res.

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The translational regulation of maternal mRNAs in time and space

Winata

Korzh

2018

FEBS Letters

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Since their discovery, the study of maternal mRNAs has led to the identification of mechanisms underlying their spatiotemporal regulation within the context of oogenesis and early embryogenesis. Following synthesis in the oocyte, maternal mRNAs are translationally silenced and sequestered into storage in cytoplasmic granules. At the same time, their unique distribution patterns throughout the oocyte and embryo are tightly controlled and connected to their functions in downstream embryonic processes. At certain points in oogenesis and early embryogenesis, maternal mRNAs are translationally activated to perform their functions in a timely manner. The cytoplasmic polyadenylation machinery is responsible for the translational activation of maternal mRNAs, and its role in initiating the maternal to zygotic transition events has recently come to light. Here, we summarize the current knowledge on maternal mRNA regulation, with particular focus on cytoplasmic polyadenylation as a mechanism for translational regulation.

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Egg Activation

Zhang

Wolfner

Williams

2018

Encyclopedia of Life Sciences

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Egg activation is the process of converting the female gamete, known as an oocyte or egg, into a cell that can support embryogenesis. In many organisms, this process is triggered by the fertilising sperm, but some organisms trigger egg activation by other mechanisms. Here we review the physiological state of the egg before activation, the mechanisms used to initiate egg activation, and the downstream cellular changes that must occur for a successful transition into a developing embryo. We will consider egg activation as it occurs in both invertebrate and vertebrate model systems, highlighting key similarities and differences between them. Key Concepts Animal eggs must undergo a process of ‘activation’ to allow them to initiate embryo development. Egg activation transitions a mature – but arrested – oocyte to a totipotent cell that can initiate mitosis and embryogenesis. Activation is triggered by a rise in calcium that sweeps across the egg in wave(s). The calcium wave is triggered by fertilisation in vertebrates, echinoderms, and molluscs and by sperm‐independent mechanical triggers in insects. The calcium wave is propagated through release of calcium from internal stores. The calcium rise triggers events including completion of meiosis, reorganisation of the sperm nucleus into a male pronucleus, translation of some stored maternal mRNAs and destruction of others in the egg, modulation of the phosphoproteome of the egg, and modification of the egg's membranes and external coverings to block fertilisation by additional sperm.

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mRNA poly(A)-tail changes specified by deadenylation broadly reshape translation in Drosophila oocytes and early embryos

Cited by 154 publications

References 54 publications

Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition

Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition

The translational regulation of maternal mRNAs in time and space

Egg Activation

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