A Cup Full of Functions

Piccioni, Federica; Zappavigna, Vincenzo; Verrotti, Arturo C.

doi:10.4161/rna.2.4.2416

Cited by 20 publications

(23 citation statements)

References 20 publications

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“…In contrast, the Orb2 dataset showed overall enrichment for G-containing motifs. A more detailed comparison of individual motif types shows that the Orb dataset is enriched in CPE variants containing A in the fifth position [TTTT(A) [1][2][3] T], whereas the TTTTGT and TTTTAAAT motifs are the most enriched in the Orb2 dataset (Fig. 3C); this difference could explain the difficulty in resolving the fifth nucleotide in de novo analysis.…”

Section: Resultsmentioning

confidence: 99%

“…This mechanism of gene-expression regulation is essential for many biological processes, including the production of gametes (1), animal development (2,3), and maintaining tissue polarity in adult organisms (2,4). In the nervous system local protein synthesis is critical for the development of highly polarized cells such as neurons (5) and is necessary for dynamic changes in neural architecture in adulthood (6) including those that take place during long-term memory (LTM) formation (7).…”

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confidence: 99%

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RNA-binding profiles of Drosophila CPEB proteins Orb and Orb2

Stepien

Oppitz

Gerlach

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Localized protein translation is critical in many biological contexts, particularly in highly polarized cells, such as neurons, to regulate gene expression in a spatiotemporal manner. The cytoplasmic polyadenylation element-binding (CPEB) family of RNA-binding proteins has emerged as a key regulator of mRNA transport and local translation required for early embryonic development, synaptic plasticity, and long-term memory (LTM). Drosophila Orb and Orb2 are single members of the CPEB1 and CPEB2 subfamilies of the CPEB proteins, respectively. At present, the identity of the mRNA targets they regulate is not fully known, and the binding specificity of the CPEB2 subfamily is a matter of debate. Using transcriptome-wide UV cross-linking and immunoprecipitation, we define the mRNA-binding sites and targets of Drosophila CPEBs. Both Orb and Orb2 bind linear cytoplasmic polyadenylation element-like sequences in the 3′ UTRs of largely overlapping target mRNAs, with Orb2 potentially having a broader specificity. Both proteins use their RNA-recognition motifs but not the Zinc-finger region for RNA binding. A subset of Orb2 targets is translationally regulated in cultured S2 cells and fly head extracts. Moreover, pan-neuronal RNAi knockdown of these targets suggests that a number of these targets are involved in LTM. Our results provide a comprehensive list of mRNA targets of the two CPEB proteins in Drosophila, thus providing insights into local protein synthesis involved in various biological processes, including LTM.CPEB | CLIP | Orb2 | translation | long-term memory

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

RNA-binding profiles of Drosophila CPEB proteins Orb and Orb2

Stepien

Oppitz

Gerlach

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…The importance of 3′UTRs and the RBPs bound to them in regulating the translation of germline transcripts is well established in C. elegans and Drosophila (Wilkie et al, 2003;Piccioni et al, 2005;Merritt et al, 2008). However, the mechanism by which the cohort of maternally supplied RBPs specifies cell fate in early C. elegans embryos via the translational regulation of multiple shared targets remains largely unknown.…”

Section: ′Utrs As Post-transcriptional Enhancersmentioning

confidence: 99%

Regulation of maternal Wnt mRNA translation inC. elegansembryos

et al. 2013

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The restricted spatiotemporal translation of maternal mRNAs, which is crucial for correct cell fate specification in early C. elegans embryos, is regulated primarily through the 3′UTR. Although genetic screens have identified many maternally expressed cell fatecontrolling RNA-binding proteins (RBPs), their in vivo targets and the mechanism(s) by which they regulate these targets are less clear. These RBPs are translated in oocytes and localize to one or a few blastomeres in a spatially and temporally dynamic fashion unique for each protein and each blastomere. Here, we characterize the translational regulation of maternally supplied mom-2 mRNA, which encodes a Wnt ligand essential for two separate cell-cell interactions in early embryos. A GFP reporter that includes only the mom-2 3′UTR is translationally repressed properly in oocytes and early embryos, and then correctly translated only in the known Wnt signaling cells. We show that the spatiotemporal translation pattern of this reporter is regulated combinatorially by a set of nine maternally supplied RBPs. These nine proteins all directly bind the mom-2 3′UTR in vitro and function as positive or negative regulators of mom-2 translation in vivo. The net translational readout for the mom-2 3′UTR reporter is determined by competitive binding between positive-and negativeacting RBPs for the 3′UTR, along with the distinct spatiotemporal localization patterns of these regulators. We propose that the 3′UTR of maternal mRNAs contains a combinatorial code that determines the topography of associated RBPs, integrating positive and negative translational inputs.

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“…Of note, the dGALT gene is located entirely within the second intron of another gene, cup (Keyes and Spradling, 1997). cup is required for ovarian function and egg production in flies; female flies that are deficient in cup are infertile and fail to lay embryos (Keyes and Spradling, 1997) (for a review, see Piccioni et al, 2005).…”

Section: Melanogaster Metabolize Galactose Via the Leloir Pathwaymentioning

confidence: 99%

A Drosophila melanogaster model of classic galactosemia

Kushner

Ryan²,

Sefton

et al. 2010

Disease Models &Amp; Mechanisms

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SUMMARYClassic galactosemia is a potentially lethal disorder that results from profound impairment of galactose-1-phosphate uridylyltransferase (GALT). Despite decades of research, the underlying pathophysiology of classic galactosemia remains unclear, in part owing to the lack of an appropriate animal model. Here, we report the establishment of a Drosophila melanogaster model of classic galactosemia; this is the first whole-animal genetic model to mimic aspects of the patient phenotype. Analogous to humans, GALT-deficient D. melanogaster survive under conditions of galactose restriction, but accumulate elevated levels of galactose-1-phosphate and succumb during larval development following galactose exposure. As in patients, the potentially lethal damage is reversible if dietary galactose restriction is initiated early in life. GALT-deficient Drosophila also exhibit locomotor complications despite dietary galactose restriction, and both the acute and long-term complications can be rescued by transgenic expression of human GALT. Using this new Drosophila model, we have begun to dissect the timing, extent and mechanism(s) of galactose sensitivity in the absence of GALT activity.

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A Cup Full of Functions

Cited by 20 publications

References 20 publications

RNA-binding profiles of Drosophila CPEB proteins Orb and Orb2

RNA-binding profiles of Drosophila CPEB proteins Orb and Orb2

Regulation of maternal Wnt mRNA translation inC. elegansembryos

A Drosophila melanogaster model of classic galactosemia

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