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Telomeric 8-Oxoguanine Drives Rapid Premature Senescence in the Absence of Telomere Shortening

ABSTRACT: Telomeric 8-Oxoguanine Drives Rapid Premature Senescence in the Absence of Telomere Shortening

PROVIDER: PRJNA733186 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14668401_1.fastq.gz	Fastqsanger.gz
	SRR14668401_2.fastq.gz	Fastqsanger.gz
	SRR14668402_1.fastq.gz	Fastqsanger.gz
	SRR14668402_2.fastq.gz	Fastqsanger.gz
	SRR14668403_1.fastq.gz	Fastqsanger.gz

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Project description:Background. Telomeric small RNAs related to PIWI-interacting RNAs (piRNAs) have been described in various eukaryotes; however, their role in germline-specific telomere function remains poorly understood. Using a Drosophila model, we performed an in-depth study of the biogenesis of telomeric piRNAs and their function in telomere homeostasis in the germline. Results To fully characterize telomeric piRNA clusters, we integrated the data obtained from analysis of endogenous telomeric repeats, as well as transgenes inserted into different telomeric and subtelomeric regions. The small RNA-seq data from strains carrying telomeric transgenes demonstrated that all transgenes belong to a class of dual-strand piRNA clusters; however, their capacity to produce piRNAs varies significantly. Rhino, a paralog of heterochromatic protein 1 (HP1) expressed exclusively in the germline, is associated with all telomeric transgenes, but its enrichment correlates with the abundance of transgenic piRNAs. It is likely that this heterogeneity is determined by the sequence peculiarities of telomeric retrotransposons. In contrast to the heterochromatic non-telomeric germline piRNA clusters, piRNA loss leads to a dramatic decrease in HP1, Rhino, and trimethylated histone H3 lysine 9 in telomeric regions. Therefore, the presence of piRNAs is required for the maintenance of telomere chromatin in the germline. Moreover, piRNA loss causes telomere translocation from the nuclear periphery toward the nuclear interior but does not affect telomere end capping. Analysis of the telomere-associated sequences (TASs) chromatin revealed strong tissue specificity. In the germline, TASs are enriched with HP1 and Rhino, in contrast to somatic tissues, where they are repressed by Polycomb group proteins. Conclusions piRNAs play an essential role in the assembly of telomeric chromatin, as well as in nuclear telomere positioning in the germline. Telomeric arrays and TASs belong to a unique type of Rhino-dependent piRNA clusters with transcripts that serve simultaneously as piRNA precursors and as their only targets. Telomeric chromatin is highly sensitive to piRNA loss, implying the existence of a novel developmental checkpoint that depends on telomere integrity in the germline.

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Telomeric 8-Oxoguanine Drives Rapid Premature Senescence in the Absence of Telomere Shortening

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