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Topoisomerase 3B Interacts with RNAi Machinery to Promote Heterochromatin Formation and Transcriptional Silencing

ABSTRACT: Topoisomerase 3B Interacts with RNAi Machinery to Promote Heterochromatin Formation and Transcriptional Silencing

PROVIDER: PRJNA488415 | ENA |

REPOSITORIES: ENA

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Topoisomerase 3B Interacts with RNAi Machinery to Promote Heterochromatin Formation and Transcriptional Silencing

Project description:Topoisomerases solve topological problems during DNA metabolism, but whether they participate in RNA metabolism remains unclear. Top3b represents a new family of topoisomerases carrying activities for both DNA and RNA. Here we show that in Drosophila, Top3b interacts biochemically and genetically with the RNAi-induced silencing complex (RISC) containing AGO2, p68 RNA helicase, and FMRP. Top3b and RISC mutants are defective in heterochromatin formation and transcriptional silencing by position-effect variegation assay; and this defect is suppressed in their double mutants. Moreover, both Top3b and AGO2 single mutants exhibit reduced heterochromatin protein HP1 in pericentric heterochromatin; and this reduction is also suppressed in their double mutant. Furthermore, expression of several genes and transposable elements (TEs) in heterochromatin is increased in the Top3b mutant. Notably, Top3b mutants defective in either RNA binding or catalytic activity are deficient in promoting HP1 recruitment and silencing of TEs. Our data suggest that Top3b acts as an RNA topoisomerase in siRNA-guided heterochromatin formation and transcriptional silencing. Grant title: An RNA topoisomerase complex interacts with Fragile X syndrome protein to promote neurodevelopment and maintain normal life-span. Grant ID: AG000689-08. Source: NIA/NIH

2018-08-29 | GSE119185 | GEO

Topoisomerase 3β Interacts with RNAi Machinery to Promote Heterochromatin Formation and Transcriptional Silencing in Drosophila

Project description:Topoisomerase 3β Interacts with RNAi Machinery to Promote Heterochromatin Formation and Transcriptional Silencing in Drosophila

| PRJNA490272 | ENA

Topoisomerase 3β Interacts with RNAi Machinery to Promote Heterochromatin Formation and Transcriptional Silencing in Drosophila [ChIP-Seq]

Project description:Topoisomerase 3β Interacts with RNAi Machinery to Promote Heterochromatin Formation and Transcriptional Silencing in Drosophila [ChIP-Seq]

| PRJNA490276 | ENA

Topoisomerase 3β Interacts with RNAi Machinery to Promote Heterochromatin Formation and Transcriptional Silencing in Drosophila [RNA-Seq]

Project description:Topoisomerase 3β Interacts with RNAi Machinery to Promote Heterochromatin Formation and Transcriptional Silencing in Drosophila [RNA-Seq]

| PRJNA490274 | ENA

Topoisomerase 3β Interacts with RNAi Machinery to Promote Heterochromatin Formation and Transcriptional Silencing in Drosophila [ChIP-Seq]

Project description:Topoisomerases solve topological problems during DNA metabolism, but whether they participate in RNA metabolism remains unclear. Top3b represents a family of topoisomerases carrying activities for both DNA and RNA. Here we show that in Drosophila, Top3b interacts biochemically and genetically with the RNAi-induced silencing complex (RISC) containing AGO2, p68 RNA helicase, and FMRP. Top3b and RISC mutants are similarly defective in heterochromatin formation and transcriptional silencing by position-effect variegation assay. Moreover, both Top3b and AGO2 mutants exhibit reduced levels of heterochromatin protein HP1 in pericentric heterochromatin. Furthermore, expression of several genes and transposable elements in heterochromatin is increased in the Top3b mutant. Notably, Top3b mutants defective in either RNA binding or catalytic activity are deficient in promoting HP1 recruitment and silencing of transposable elements. Our data suggest that Top3b may act as an RNA topoisomerase in siRNA-guided heterochromatin formation and transcriptional silencing.

2018-09-12 | GSE119777 | GEO

Topoisomerase 3β Interacts with RNAi Machinery to Promote Heterochromatin Formation and Transcriptional Silencing in Drosophila [RNA-Seq]

Project description:Topoisomerases solve topological problems during DNA metabolism, but whether they participate in RNA metabolism remains unclear. Top3b represents a family of topoisomerases carrying activities for both DNA and RNA. Here we show that in Drosophila, Top3b interacts biochemically and genetically with the RNAi-induced silencing complex (RISC) containing AGO2, p68 RNA helicase, and FMRP. Top3b and RISC mutants are similarly defective in heterochromatin formation and transcriptional silencing by position-effect variegation assay. Moreover, both Top3b and AGO2 mutants exhibit reduced levels of heterochromatin protein HP1 in pericentric heterochromatin. Furthermore, expression of several genes and transposable elements in heterochromatin is increased in the Top3b mutant. Notably, Top3b mutants defective in either RNA binding or catalytic activity are deficient in promoting HP1 recruitment and silencing of transposable elements. Our data suggest that Top3b may act as an RNA topoisomerase in siRNA-guided heterochromatin formation and transcriptional silencing.

2018-09-12 | GSE119626 | GEO

Topoisomerase 3β interacts with RNAi machinery to promote heterochromatin formation and transcriptional silencing in Drosophila.

Project description: Not available

| S-EPMC6251927 | biostudies-literature

Topoisomerase 3β Interacts with RNAi Machinery to Promote Heterochromatin Formation and Transcriptional Silencing in Drosophila

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-09-12 | GSE119736 | GEO

Topoisomerase 3b is essential for neuronal activity-dependent transcription, neurogenesis, and synaptic and behavioral neuroplasticity

Project description:Topoisomerase 3b (Top3b) is the only dual-activity topoisomerase in animals that can change topology for both DNA and RNA, and facilitate transcription on DNA and translation on mRNAs. Top3b mutation has been linked to schizophrenia, autism, epilepsy, and cognitive impairment. However, whether and how Top3b mutations are causal to these disorders remain unclear. Here we show that Top3b knockout mice exhibit behavioral phenotypes related to psychiatric disorders and cognitive impairment, including increased anxiety and fear, abnormal social interactions, impaired context discrimination, and defective spatial learning and memory. In addition, these mice display deficits in adult hippocampal neurogenesis and synaptic plasticity. Notably, the brains of the mutant mice exhibit impaired global neuronal activity-dependent transcription in response to fear conditioning stress, and the affected genes include many that are critical for neuronal functions and mental health. Our data suggest that Top3b is essential for normal brain function in multiple domains, and defective neuronal activity-dependent transcription may be a mechanism by which Top3b deletion causes cognitive impairment and psychiatric disorders.

2020-05-22 | GSE145730 | GEO

Topoisomerase 3b is essential for neuronal activity-dependent transcription, neurogenesis, and synaptic and behavioral neuroplasticity

Project description:Topoisomerase 3b is essential for neuronal activity-dependent transcription, neurogenesis, and synaptic and behavioral neuroplasticity

| PRJNA608010 | ENA

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