Blanks, a nuclear siRNA/dsRNA-binding complex component, is required for
            <i>Drosophila</i>
            spermiogenesis

Gerbasi, Vincent R.; Preall, Jonathan; Golden, Daniel E.; Powell, David W.; Cummins, Timothy D.; Sontheimer, Erik J.

doi:10.1073/pnas.1009781108

Cited by 33 publications

(42 citation statements)

References 59 publications

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“…We have ruled out R2D2 as a potential substitute. Several other dsRBPs are encoded in the Drosophila genome, and two of these were found to interact with Dcr-2, but they are unlikely to mediate a global antiviral response since their expression is restricted to the male testis [53]. Moreover, no dsRBP gene other than R2D2 has been identified as rapidly evolving as Dcr-2 and Ago2 [51].…”

Section: Discussionmentioning

confidence: 99%

Functional Specialization of the Small Interfering RNA Pathway in Response to Virus Infection

et al. 2013

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In Drosophila, post-transcriptional gene silencing occurs when exogenous or endogenous double stranded RNA (dsRNA) is processed into small interfering RNAs (siRNAs) by Dicer-2 (Dcr-2) in association with a dsRNA-binding protein (dsRBP) cofactor called Loquacious (Loqs-PD). siRNAs are then loaded onto Argonaute-2 (Ago2) by the action of Dcr-2 with another dsRBP cofactor called R2D2. Loaded Ago2 executes the destruction of target RNAs that have sequence complementarity to siRNAs. Although Dcr-2, R2D2, and Ago2 are essential for innate antiviral defense, the mechanism of virus-derived siRNA (vsiRNA) biogenesis and viral target inhibition remains unclear. Here, we characterize the response mechanism mediated by siRNAs against two different RNA viruses that infect Drosophila. In both cases, we show that vsiRNAs are generated by Dcr-2 processing of dsRNA formed during viral genome replication and, to a lesser extent, viral transcription. These vsiRNAs seem to preferentially target viral polyadenylated RNA to inhibit viral replication. Loqs-PD is completely dispensable for silencing of the viruses, in contrast to its role in silencing endogenous targets. Biogenesis of vsiRNAs is independent of both Loqs-PD and R2D2. R2D2, however, is required for sorting and loading of vsiRNAs onto Ago2 and inhibition of viral RNA expression. Direct injection of viral RNA into Drosophila results in replication that is also independent of Loqs-PD. This suggests that triggering of the antiviral pathway is not related to viral mode of entry but recognition of intrinsic features of virus RNA. Our results indicate the existence of a vsiRNA pathway that is separate from the endogenous siRNA pathway and is specifically triggered by virus RNA. We speculate that this unique framework might be necessary for a prompt and efficient antiviral response.

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Section: Discussionmentioning

confidence: 99%

Functional Specialization of the Small Interfering RNA Pathway in Response to Virus Infection

et al. 2013

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“…NSun2 generally localizes to cellular RNA-processing centers, and while NSun2 is the first RNA methyltransferase identified as a component of the chromatoid body, Drosophila NSun2 is also a component of ribonuclear particles involved in RNA silencing and germ cell development (58). How NSun2 mechanistically blocks the progression of the first prophase of male meiosis before the pachytene stage remains to be determined but may, at least in part, be dependent on its tRNA methyltransferase activity.…”

Section: Discussionmentioning

confidence: 99%

The Mouse Cytosine-5 RNA Methyltransferase NSun2 Is a Component of the Chromatoid Body and Required for Testis Differentiation

Hussain

Tuorto

Menon

et al. 2013

Molecular and Cellular Biology

134

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dPosttranscriptional regulatory mechanisms are crucial for protein synthesis during spermatogenesis and are often organized by the chromatoid body. Here, we identify the RNA methyltransferase NSun2 as a novel component of the chromatoid body and, further, show that NSun2 is essential for germ cell differentiation in the mouse testis. In NSun2-depleted testes, genes encoding Ddx4, Miwi, and Tudor domain-containing (Tdr) proteins are repressed, indicating that RNA-processing and posttranscriptional pathways are impaired. Loss of NSun2 specifically blocked meiotic progression of germ cells into the pachytene stage, as spermatogonial and Sertoli cells were unaffected in knockout mice. We observed the same phenotype when we simultaneously deleted NSun2 and Dnmt2, the only other cytosine-5 RNA methyltransferase characterized to date, indicating that Dnmt2 was not functionally redundant with NSun2 in spermatogonial stem cells or Sertoli cells. Specific NSun2-and Dnmt2-methylated tRNAs decreased in abundance when both methyltransferases were deleted, suggesting that RNA methylation pathways play an essential role in male germ cell differentiation.

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“…In addition to dHP1c, WOC and ROW, these experiments detected the dHP1b isoform 34 ; the boundary protein BEAF- 32 (ref. 35); the chromosomal proteins Chromator and Z4, which are known to form a complex 36,37 ; the RNA-binding protein Blanks 38 ; the ubiquitin receptor protein dDsk2; and coilin, a factor that marks Cajal bodies and associates to the histone locus 39 . Co-IP experiments directly confirmed several of these interactions.…”

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confidence: 99%

dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes

et al. 2015

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dDsk2 is a conserved extraproteasomal ubiquitin receptor that targets ubiquitylated proteins for degradation. Here we report that dDsk2 plays a nonproteolytic function in transcription regulation. dDsk2 interacts with the dHP1c complex, localizes at promoters of developmental genes and is required for transcription. Through the ubiquitin-binding domain, dDsk2 interacts with H2Bub1, a modification that occurs at dHP1c complex-binding sites. H2Bub1 is not required for binding of the complex; however, dDsk2 depletion strongly reduces H2Bub1. Co-depletion of the H2Bub1 deubiquitylase dUbp8/Nonstop suppresses this reduction and rescues expression of target genes. RNA polymerase II is strongly paused at promoters of dHP1c complex target genes and dDsk2 depletion disrupts pausing. Altogether, these results suggest that dDsk2 prevents dUbp8/Nonstop-dependent H2Bub1 deubiquitylation at promoters of dHP1c complex target genes and regulates RNA polymerase II pausing. These results expand the catalogue of nonproteolytic functions of ubiquitin receptors to the epigenetic regulation of chromatin modifications.

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Blanks, a nuclear siRNA/dsRNA-binding complex component, is required for Drosophila spermiogenesis

Cited by 33 publications

References 59 publications

Functional Specialization of the Small Interfering RNA Pathway in Response to Virus Infection

Functional Specialization of the Small Interfering RNA Pathway in Response to Virus Infection

The Mouse Cytosine-5 RNA Methyltransferase NSun2 Is a Component of the Chromatoid Body and Required for Testis Differentiation

dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes

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