Squid, Cup, and PABP55B function together to regulate gurken translation in Drosophila

Clouse, Kate; Ferguson, Scott B.; Schüpbach, Trudi

doi:10.1016/j.ydbio.2007.11.008

Cited by 65 publications

(78 citation statements)

References 67 publications

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“…take on a role that is distinct from Hnrpab1, such as regulating translation or mRNA stability in this compartment. Similar to Hnrpab, multiple isoforms of the Drosophila Squid protein have distinct roles in mRNA localization and translation (Norvell et al 1999(Norvell et al , 2005Clouse et al 2008). It will be worthwhile to delineate the mechanism of how Hnrpab1 and Hnrpab2 are targeted to the nucleus, how the mechanism of localization for each isoform is regulated during neuronal development, and what role Hnrpab1's unique exon 7 plays in regulating this activity.…”

Section: The Nucleo-cytoplasmic Distribution Of Hnrpab Isoforms Suggementioning

confidence: 99%

Hnrpab regulates neural development and neuron cell survival after glutamate stimulation

Sinnamon¹,

Waddell²,

Nik³

et al. 2012

RNA

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The molecular mechanisms that govern the timing and fate of neural stem-cell differentiation toward the distinct neural lineages of the nervous system are not well defined. The contribution of post-transcriptional regulation of gene expression to neural stem-cell maintenance and differentiation, in particular, remains inadequately characterized. The RNA-binding protein Hnrpab is highly expressed in developing nervous tissue and in neurogenic regions of the adult brain, but its role in neural development and function is unknown. We raised a mouse that lacks Hnrpab expression to define what role, if any, Hnrpab plays during mouse neural development. We performed a genome-wide quantitative analysis of protein expression within the hippocampus of newborn mice to demonstrate significantly altered gene expression in mice lacking Hnrpab relative to Hnrpab-expressing littermates. The proteins affected suggested an altered pattern of neural development and also unexpectedly indicated altered glutamate signaling. We demonstrate that Hnrpab -/-neural stem and progenitor cells undergo altered differentiation patterns in culture, and mature Hnrpab -/-neurons demonstrate increased sensitivity to glutamate-induced excitotoxicity. We also demonstrate that Hnrpab nucleocytoplasmic distribution in primary neurons is regulated by developmental stage.

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Section: The Nucleo-cytoplasmic Distribution Of Hnrpab Isoforms Suggementioning

confidence: 99%

Hnrpab regulates neural development and neuron cell survival after glutamate stimulation

Sinnamon¹,

Waddell²,

Nik³

et al. 2012

RNA

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“…Cup binds to eIF4E and to RNA-binding proteins that specifically recognize regions at the 39 UTRs of mRNAs. Cup is involved in repressing at least three localized and developmentally essential mRNAs in Drosophila-oskar, nanos, and gurken-and might function as a general repressor for many as-yet-unknown mRNAs (Schüpbach and Wieschaus 1991;Keyes and Spradling 1997;Verrotti and Wharton 2000;Wilhelm et al 2003;Nakamura et al 2004;Nelson et al 2004;Zappavigna et al 2004;Clouse et al 2008). According to the current model, Cup is recruited to the 39 UTRs of mRNA targets via different adaptor/repressor proteins that bind specifically to sequence/structure elements on the RNA.…”

mentioning

confidence: 99%

Crystal structure of a minimal eIF4E–Cup complex reveals a general mechanism of eIF4E regulation in translational repression

Kinkelin

Veith

Grünwald

et al. 2012

RNA

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Cup is an eIF4E-binding protein (4E-BP) that plays a central role in translational regulation of localized mRNAs during early Drosophila development. In particular, Cup is required for repressing translation of the maternally contributed oskar, nanos, and gurken mRNAs, all of which are essential for embryonic body axis determination. Here, we present the 2.8 Å resolution crystal structure of a minimal eIF4E-Cup assembly, consisting of the interacting regions of the two proteins. In the structure, two separate segments of Cup contact two orthogonal faces of eIF4E. The eIF4E-binding consensus motif of Cup (YXXXXLF) binds the convex side of eIF4E similarly to the consensus of other eIF4E-binding proteins, such as 4E-BPs and eIF4G. The second, noncanonical, eIF4E-binding site of Cup binds laterally and perpendicularly to the eIF4E b-sheet. Mutations of Cup at this binding site were shown to reduce binding to eIF4E and to promote the destabilization of the associated mRNA. Comparison with the binding mode of eIF4G to eIF4E suggests that Cup and eIF4G binding would be mutually exclusive at both binding sites. This shows how a common molecular surface of eIF4E might recognize different proteins acting at different times in the same pathway. The structure provides insight into the mechanism by which Cup disrupts eIF4E-eIF4G interaction and has broader implications for understanding the role of 4E-BPs in translational regulation.

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“…Osk contributes to derepressing nos by preventing its association with Smaug, and thus with CCR4 deadenylase (Zaessinger et al 2006). Activation of grk mRNA translation at the antero-dorsal cortex of the developing oocyte is mediated by poly(A)-binding protein 55D (PABP55D) in association with Encore (Clouse et al 2008).…”

mentioning

confidence: 99%

Vasa promotes Drosophila germline stem cell differentiation by activating mei-P26 translation by directly interacting with a (U)-rich motif in its 3′ UTR

Liu

Han²,

Lasko³

2009

Genes Dev.

104

105

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Vasa (Vas) is a DEAD-box RNA-binding protein required in Drosophila at several steps of oogenesis and for primordial germ cell (PGC) specification. Vas associates with eukaryotic initiation factor 5B (eIF5B), and this interaction has been implicated in translational activation of gurken mRNA in the oocyte. Vas is expressed in all ovarian germline cells, and aspects of the vas-null phenotype suggest a function in regulating the balance between germline stem cells (GSCs) and their fate-restricted descendants. We used a biochemical approach to recover Vas-associated mRNAs and obtained mei-P26, whose product represses microRNA activity and promotes GSC differentiation. We found that vas and mei-P26 mutants interact, and that mei-P26 translation is substantially reduced in vas mutant cells. In vitro, Vas protein bound specifically to a (U)-rich motif in the mei-P26 39 untranslated region (UTR), and Vas-dependent regulation of GFP-mei-P26 transgenes in vivo was dependent on the same (U)-rich 39 UTR domain. The ability of Vas to activate mei-P26 expression in vivo was abrogated by a mutation that greatly reduces its interaction with eIF5B. Taken together, our data support the conclusion that Vas promotes germ cell differentiation by directly activating mei-P26 translation in early-stage committed cells.[Keywords: Oogenesis; RNA-binding protein; DEAD-box; patterning; development] Supplemental material is available at http://www.genesdev.org.

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Squid, Cup, and PABP55B function together to regulate gurken translation in Drosophila

Cited by 65 publications

References 67 publications

Hnrpab regulates neural development and neuron cell survival after glutamate stimulation

Hnrpab regulates neural development and neuron cell survival after glutamate stimulation

Crystal structure of a minimal eIF4E–Cup complex reveals a general mechanism of eIF4E regulation in translational repression

Vasa promotes Drosophila germline stem cell differentiation by activating mei-P26 translation by directly interacting with a (U)-rich motif in its 3′ UTR

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