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RNA Targets and Function of Topoisomerase 3β in Reducing Stress in Neuronal Physiology

ABSTRACT: RNA Targets and Function of Topoisomerase 3β in Reducing Stress in Neuronal Physiology

PROVIDER: PRJNA1049014 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27103912_1.fastq.gz	Fastqsanger.gz
	SRR27103912_2.fastq.gz	Fastqsanger.gz
	SRR27103913_1.fastq.gz	Fastqsanger.gz
	SRR27103913_2.fastq.gz	Fastqsanger.gz
	SRR27103914_1.fastq.gz	Fastqsanger.gz

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RNA Targets and Function of Topoisomerase 3β in Reducing Stress in Neuronal Physiology

Project description:Topoisomerase 3β (Top3β) relaxes DNA and RNA and its dysregulation is implicated in various neurodevelopmental and cognitive disorders. We developed a novel protocol to isolate RNA targets of the topoisomerase without artificial cross-linking and used it to identify the RNA targets of Top3β. Lack of the enzymatic activity of Top3β affects gene expression of (pre)mRNAs with the characteristics described for the Top3β targets and we found evidence that this might also apply to several neurological diseases and cancers with which human Top3β was associated.

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

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A dual-activity topoisomerase complex regulates mRNA translation and turnover

Project description:Topoisomerase 3β (TOP3B) and TDRD3 form a dual-activity topoisomerase complex that interacts with FMRP and can change the topology of both DNA and RNA. Here, we investigated the post-transcriptional influence of TOP3B and associated proteins on mRNA translation and turnover. First, we discovered that in human HCT116 colon cancer cells, knock-out (KO) of TOP3B had similar effects on mRNA turnover and translation as did TDRD3-KO, while FMRP-KO resulted in rather distinct effects, indicating that TOP3B had stronger coordination with TDRD3 than FMRP in mRNA regulation. Second, we identified TOP3B-bound mRNAs in HCT116 cells; we found that while TOP3B did not directly influence the stability or translation of most TOP3B target mRNAs, it stabilized a subset of target mRNAs but had a more complex effect on translation--enhancing for some mRNAs whereas reducing for others. Interestingly, a point mutation that specifically disrupted TOP3B catalytic activity only partially recapitulated the effects of TOP3B-KO on mRNA stability and translation, suggesting that the impact of TOP3B on target mRNAs is only in part linked to its ability to change topology of mRNAs. Collectively, our data suggest that TOP3B-TDRD3 can regulate mRNA translation and turnover by mechanisms that are dependent and independent of topoisomerase activity.

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