<i>Drosophila</i>
            Dicer-2 has an RNA interference–independent function that modulates Toll immune signaling

Wang, Zhaowei; Wu, Di; Liu, Yongxiang; Xia, Xiaoling; Gong, Weibin; Qiu, Yang; Yang, Jie; Zheng, Ya Ying; Li, Jingjing; Wang, Yufeng; Xiang, Ye; Hu, Yuanyang; Zhou, Xi

doi:10.1126/sciadv.1500228

Cited by 43 publications

(32 citation statements)

References 50 publications

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“…Our data are in agreement with recent findings of an RNAi-independent function of Dicer-2 in Toll immune signaling, where Dicer-2 was found to increase the translation of Toll mRNA and promote resistance to fungal infection (Wang et al 2015). We provide here a molecular mechanism for translational control by Dicer-2 in embryos.…”

Section: Discussionsupporting

confidence: 92%

“…Binding of Wispy to PR is consistent with its role in Toll mRNA polyadenylation, and suggests that important transacting factors recruit Wispy to this region. Dicer-2 (Dcr-2) has been previously shown to promote the translation of Toll mRNA during immune signaling by binding to its 3 ′ UTR (Wang et al 2015), suggesting that Dicer-2 could be the Wispy recruiting factor and that cytoplasmic polyadenylation may underlie the effects of Dicer-2 on translation. In support of this hypothesis, recombinant Dicer-2 binds to PR in electrophoretic mobility shift assays, yielding a complex that is competed by excess PR but not by F1 ( Fig.…”

Section: Dicer-2 Associates With Cytoplasmic Polyadenylation Substratesmentioning

confidence: 99%

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Dicer-2 promotes mRNA activation through cytoplasmic polyadenylation

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Guitart

Villalba

et al. 2018

RNA

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Cytoplasmic polyadenylation is a widespread mechanism to regulate mRNA translation. In vertebrates, this process requires two sequence elements in target 3 ′ ′ ′ ′ ′ UTRs: the U-rich cytoplasmic polyadenylation element and the AAUAAA hexanucleotide. In Drosophila melanogaster, cytoplasmic polyadenylation of Toll mRNA occurs independently of these canonical elements and requires a machinery that remains to be characterized. Here we identify Dicer-2 as a component of this machinery. Dicer-2, a factor previously involved in RNA interference (RNAi), interacts with the cytoplasmic poly(A) polymerase Wispy. Depletion of Dicer-2 from polyadenylation-competent embryo extracts and analysis of wispy mutants indicate that both factors are necessary for polyadenylation and translation of Toll mRNA. We further identify r2d2 mRNA, encoding a Dicer-2 partner in RNAi, as a Dicer-2 polyadenylation target. Our results uncover a novel function of Dicer-2 in activation of mRNA translation through cytoplasmic polyadenylation.

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Section: Discussionsupporting

confidence: 92%

Section: Dicer-2 Associates With Cytoplasmic Polyadenylation Substratesmentioning

confidence: 99%

Dicer-2 promotes mRNA activation through cytoplasmic polyadenylation

Coll

Guitart

Villalba

et al. 2018

RNA

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“…The samples were electrophoresed on 1.5% agaroseformaldehyde denaturing gels and transferred onto N ϩ nylon membranes (Roche). The RdRP products were detected via Northern blots that were performed according to our standard procedures (62). The probe for the Northern blots is listed in Table 1.…”

Section: Discussionmentioning

confidence: 99%

Human Norovirus NS3 Has RNA Helicase and Chaperoning Activities

Hosmillo

Schwanke

et al. 2018

J Virol

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RNA-remodeling proteins, including RNA helicases and chaperones, act to remodel RNA structures and/or protein-RNA interactions and are required for all processes involving RNAs. Although many viruses encode RNA helicases and chaperones, their activities and their roles in infected cells largely remain elusive. Noroviruses are a diverse group of positive-strand RNA viruses in the family and constitute a significant and potentially fatal threat to human health. Here, we report that the protein NS3 encoded by human norovirus has both ATP-dependent RNA helicase activity that unwinds RNA helices and ATP-independent RNA-chaperoning activity that can remodel structured RNAs and facilitate strand annealing. Moreover, NS3 can facilitate viral RNA synthesis by norovirus polymerase. NS3 may therefore play an important role in norovirus RNA replication. Lastly, we demonstrate that the RNA-remodeling activity of NS3 is inhibited by guanidine hydrochloride, an FDA-approved compound, and, more importantly, that it reduces the replication of the norovirus replicon in cultured human cells. Altogether, these findings are the first to demonstrate the presence of RNA-remodeling activities encoded by and highlight the functional significance of NS3 in the noroviral life cycle. Noroviruses are a diverse group of positive-strand RNA viruses, which annually cause hundreds of millions of human infections and over 200,000 deaths worldwide. For RNA viruses, cellular or virus-encoded RNA helicases and/or chaperones have long been considered to play pivotal roles in viral life cycles. However, neither RNA helicase nor chaperoning activity has been demonstrated to be associated with any norovirus-encoded proteins, and it is also unknown whether norovirus replication requires the participation of any viral or cellular RNA helicases/chaperones. We found that a norovirus protein, NS3, not only has ATP-dependent helicase activity, but also acts as an ATP-independent RNA chaperone. Also, NS3 can facilitate viral RNA synthesis, suggesting the important role of NS3 in norovirus replication. Moreover, NS3 activities can be inhibited by an FDA-approved compound, which also suppresses norovirus replicon replication in human cells, raising the possibility that NS3 could be a target for antinoroviral drug development.

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“…This has the advantage of monitoring RNA dynamics without the potential complications associated with protein overexpression; however, if coding regions of the RNA are important for RNA metabolism or localization they would be missed. It is also possible that overexpressing a 3′UTR could titrate out RNA-binding proteins (Donnelly et al, 2013, 2011; Garcia-Gras, Chi, & Thompson, 2000; Wang et al, 2015); however, thus far evidence of such an effect in germ cells is lacking. Additionally, another application of this system would be to immunoprecipitate the tagged MCP proteins in order to identify RNA-binding proteins that associate with one’s RNA of interest in a 3′UTR-dependent manner, as has previously been demonstrated for mammalian cell culture and C. elegans (Kwak, Wang, Ballantyne, Kimble, & Wickens, 2004; Liu et al, 2015).…”

Section: Studying the Dynamic Localization Of Germ Plasm Rnasmentioning

confidence: 99%

Methods to study maternal regulation of germ cell specification in zebrafish

Kaufman

Marlow

2016

Methods in Cell Biology

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The process by which the germ line is specified in the zebrafish embryo is under the control of maternal gene products that were produced during oogenesis. Zebrafish are highly amenable to microscopic observation of the processes governing maternal germ cell specification because early embryos are transparent, and the germ line is specified rapidly (within 4–5 h post fertilization). Advantages of zebrafish over other models used to study vertebrate germ cell formation include their genetic tractability, the large numbers of progeny, and the easily manipulable genome, all of which make zebrafish an ideal system for studying the genetic regulators and cellular basis of germ cell formation and maintenance. Classical molecular biology techniques, including expression analysis through in situ hybridization and forward genetic screens, have laid the foundation for our understanding of germ cell development in zebrafish. In this chapter, we discuss some of these classic techniques, as well as recent cutting-edge methodologies that have improved our ability to visualize the process of germ cell specification and differentiation, and the tracking of specific molecules involved in these processes. Additionally, we discuss traditional and novel technologies for manipulating the zebrafish genome to identify new components through loss-of-function studies of putative germ cell regulators. Together with the numerous aforementioned advantages of zebrafish as a genetic model for studying development, we believe these new techniques will continue to advance zebrafish to the forefront for investigation of the molecular regulators of germ cell specification and germ line biology.

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Drosophila Dicer-2 has an RNA interference–independent function that modulates Toll immune signaling

Abstract: Fly Dicer-2 exhibits a non–RNA interference function in the posttranscriptional modulation of Toll protein expression and Toll signaling.

Cited by 43 publications

References 50 publications

Dicer-2 promotes mRNA activation through cytoplasmic polyadenylation

Dicer-2 promotes mRNA activation through cytoplasmic polyadenylation

Human Norovirus NS3 Has RNA Helicase and Chaperoning Activities

Methods to study maternal regulation of germ cell specification in zebrafish

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