MicroRNA-8 targets the Wingless signaling pathway in the female mosquito fat body to regulate reproductive processes

Lucas, Keira J.; Roy, Sourav; Ha, Jisu; Gervaise, Amanda L.; Kokoza, Vladimir; Raikhel, Alexander S.

doi:10.1073/pnas.1424408112

Cited by 105 publications

(94 citation statements)

References 32 publications

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“…Adverse phenotypes caused by miR-309 miRNA depletion were expected to be alleviated after silencing its major target gene. Previously, phenotypic defects resulting from miRNA deletions were successfully rescued after RNAi silencing their main target genes in A. aegypti (16,17). In our rescue experiments, silencing SIX4 was able to significantly recover phenotypic manifestations caused by miR-309 depletion, such as smaller follicle size and significantly reduced egg numbers.…”

Section: Resultsmentioning

confidence: 60%

“…The mosquitospecific miR-1174 targets serine hydroxymethyltransferase to control blood intake and digestion in the gut and influences egg development (16). Moreover, the conserved miRNA miR-8 regulates the long-range Wingless signaling that is required for secretion of lipophorin and vitellogenin from the fat body in response to blood feeding, affecting deposition of yolk proteins in oocytes and fecundity of female mosquitoes (17).…”

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confidence: 99%

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microRNA-309 targets the Homeobox gene SIX4 and controls ovarian development in the mosquito Aedes aegypti

Zhang

Zhao

Roy

et al. 2016

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

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106

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Obligatory blood-triggered reproductive strategy is an evolutionary adaptation of mosquitoes for rapid egg development. It contributes to the vectorial capacity of these insects. Therefore, understanding the molecular mechanisms underlying reproductive processes is of particular importance. Here, we report that microRNA-309 (miR-309) plays a critical role in mosquito reproduction. A spatiotemporal expression profile of miR-309 displayed its blood feeding-dependent onset and ovary-specific manifestation in female Aedes aegypti mosquitoes. Antagomir silencing of miR-309 impaired ovarian development and resulted in nonsynchronized follicle growth. Furthermore, the genetic disruption of miR-309 by CRISPR/Cas9 system led to the developmental failure of primary follicle formation. Examination of genomic responses to miR-309 depletion revealed that several pathways associated with ovarian development are down-regulated. Comparative analysis of genes obtained from the high-throughput RNA sequencing of ovarian tissue from the miR-309 antagomirsilenced mosquitoes with those from the in silico computation target prediction identified that the gene-encoding SIX homeobox 4 protein (SIX4) is a putative target of miR-309. Reporter assay and RNA immunoprecipitation confirmed that SIX4 is a direct target of miR-309. RNA interference of SIX4 was able to rescue phenotypic manifestations caused by miR-309 depletion. Thus, miR-309 plays a critical role in mosquito reproduction by targeting SIX4 in the ovary and serves as a regulatory switch permitting a stage-specific degradation of the ovarian SIX4 mRNA. In turn, this microRNA (miRNA)-targeted degradation is required for appropriate initiation of a blood feeding-triggered phase of ovarian development, highlighting involvement of this miRNA in mosquito reproduction.Homeobox protein gene | microRNA | CRISPR/Cas9 | ovary | fast evolution T ransmission of mosquito-borne diseases brings enormous human suffering, with more than 1 million deaths worldwide annually. The yellow fever mosquito Aedes aegypti has reemerged as one of the most dangerous vectors of human diseases, transmitting Dengue fever, Yellow fever, Chikungunya, and Zika virus (1-4). Because of the lack of effective vaccines and increasing drug resistance in pathogens, biological control is considered one of the most promising strategies for preventing disease transmission. In particular, female hematophagous mosquitoes rely on acquisition of blood to initiate a series of physiological events promoting egg development (5, 6). Therefore, understanding the molecular mechanisms underlying ovarian activation is of great significance for the development of effective approaches to control mosquito-borne diseases (7,8).MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level through translational repression or mRNA decay (9). Hence, miRNAs play significant roles in governing multiple functions in animals and plants via integrating sophisticated miRNA-mRNA regulatory networks (10, 11...

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Section: Resultsmentioning

confidence: 60%

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confidence: 99%

microRNA-309 targets the Homeobox gene SIX4 and controls ovarian development in the mosquito Aedes aegypti

Zhang

Zhao

Roy

et al. 2016

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

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106

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“…Furthermore, miR-8-3p and miR-275-3p (ranked 11th; Dataset S1) have been shown previously to be critical in the normal progression of Ae. aegypti egg development PBM (29,31).…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies illustrated that miR-275, miR-1174, miR-8, and miR-1890 are essential for the normal progression of blood meal digestion and egg development of Ae. aegypti (29)(30)(31)(32). However, our knowledge of the role of miRNAs in posttranscriptional regulation of the FB genes affecting these tissue functions is limited.…”

Section: Significancementioning

confidence: 99%

Transcriptome-wide microRNA and target dynamics in the fat body during the gonadotrophic cycle of Aedes aegypti

Zhang

Aksoy

Girke

et al. 2017

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

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The mosquito Aedes aegypti is a major vector of numerous viral diseases, because it requires a blood meal to facilitate egg development. The fat body, a counterpart of mammalian liver and adipose tissues, is the metabolic center, playing a key role in reproduction. Therefore, understanding of regulatory networks controlling its functions is critical, and the role of microRNAs (miRNAs) in the process is largely unknown. We aimed to explore miRNA expression and potential targets in the female fat body of Ae. aegypti, as well as their changes postblood meal (PBM). Small RNA library analysis revealed five unique miRNA patterns sequentially expressed at five sampled time points, likely responding to, and affecting, waves of upstream hormonal signals and gene expression in the same period. To link miRNA identities with downstream targets, transcriptome-wide mRNA 3′ UTR interaction sites were experimentally determined at 72 h posteclosion and 24 h PBM through Argonaute 1 cross-linking and immunoprecipitation followed by high-throughput sequencing. Several target sites were validated by means of in vitro luciferase assays with wild-type and mutated 3′ UTRs for six miRNA families. With established transgenic lines, consistent results were observed with spatiotemporal knockdown of miR-8 and luciferase assays. We further investigated miRNAs potentially regulating various physiological processes based on Clusters of Orthologous Groups functional categories. Hence, the present work comprehensively elucidated miRNA expression and target dynamics in the female mosquito fat body, providing a solid foundation for future functional studies of miRNA regulation during the gonadotrophic cycle.Aedes aegypti | fat body | microRNA | microRNA targets | Argonaute 1

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“…The second highest expression is for miR‐281 with an expression value of 18,063 and might be involved in the development and metamorphosis of T. tabaci as recent studies showed that miR‐281 regulates the expression of ecdysone receptor ( EcR ) isoform B, in Bombyx mori (Jiang et al., 2013). Another interesting microRNA obtained in the current study was miR‐8, and it can target the Wingless signalling pathway to regulate secretion of yolk protein precursors by the female mosquito fat body and accumulation into the developing ovaries (Lucas et al., 2015, http://www.smartscitech.com/index.php/RD/article/view/815). Therefore, it is quite possible that miR‐8 may play a key role in the reproductive processes of T. tabaci .…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide identification, expression profiling, and target gene analysis of microRNAs in the Onion thrips, Thrips tabaci Lindeman (Thysanoptera: Thripidae), vectors of tospoviruses (Bunyaviridae)

Rebijith

Asokan

Hande

et al. 2018

Ecology and Evolution

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Thrips tabaci Lindeman is an important polyphagous insect pest species estimated to cause losses of more than U.S. $1 billion worldwide annually. Chemical insecticides are of limited use in the management of T. tabaci due to the thigmokinetic behavior and development of resistance to insecticides. There is an urgent need to find alternative management strategies. Small noncoding RNAs (sncRNAs) especially microRNAs (miRNAs) hold great promise as key regulators of gene expression in a wide range of organisms. MiRNAs are a group of endogenously originated sncRNA known to regulate gene expression in animals, plants, and protozoans. In this study, we explored these RNAs in T. tabaci using deep sequencing to provide a basis for future studies of their biological and physiological roles in governing gene expression. Apart from snoRNAs and piRNAs, our study identified nine novel and 130 known miRNAs from T. tabaci. Functional classification of the targets for these miRNAs predicted that majority are involved in regulating transcription, translation, signal transduction and genetic information processing. The higher expression of few miRNAs (such as tta‐miR‐281, tta‐miR‐184, tta‐miR‐3533, tta‐miR‐N1, tta‐miR‐N7, and tta‐miR‐N9) in T. tabaci pupal and adult stages reflected their possible role in larval and adult development, metamorphosis, parthenogenesis, and reproduction. This is the first exploration of the miRNAome in T. tabaci, which not only provides insights into their possible role in insect metamorphosis, growth, and development but also offer an important resource for future pest management strategies.

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MicroRNA-8 targets the Wingless signaling pathway in the female mosquito fat body to regulate reproductive processes

Cited by 105 publications

References 32 publications

microRNA-309 targets the Homeobox gene SIX4 and controls ovarian development in the mosquito Aedes aegypti

microRNA-309 targets the Homeobox gene SIX4 and controls ovarian development in the mosquito Aedes aegypti

Transcriptome-wide microRNA and target dynamics in the fat body during the gonadotrophic cycle of Aedes aegypti

Genome‐wide identification, expression profiling, and target gene analysis of microRNAs in the Onion thrips, Thrips tabaci Lindeman (Thysanoptera: Thripidae), vectors of tospoviruses (Bunyaviridae)

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