Project description:In metazoan gonads, transposable elements (TEs) mobilization is limited by PIWI-interacting RNAs (piRNAs). These small RNAs originate from specific source loci, the piRNA clusters. piRNAs are known to silence TEs in the cells where they are produced. Endogenous retroviruses (ERVs), a subclass of TEs, pose a particular threat because they are capable of transiting from cell to cell. In this study, we reveal that piRNAs produced locally in germ cells counteract invasion by ERVs arriving from adjacent somatic cells. We reactivated the Drosophila ERV ZAM in somatic gonadal cells by deleting, using CRISPR-Cas9 genome editing, its single copy in the somatic flamenco piRNA cluster, while keeping the piRNA pathway fully functional. Upon reactivation, ZAM invaded the oocytes, resulting in transposition and severe fertility defects. We show that once ZAM-piRNAs are produced in germ cells they counter the invasion. Our study sheds new light on the mechanisms of recognition and regulation of invasive genetic elements, which is essential for the maintenance of genome integrity.
Project description:In metazoan gonads, transposable elements (TEs) mobilization is limited by PIWI-interacting RNAs (piRNAs). These small RNAs originate from specific source loci, the piRNA clusters. piRNAs are known to silence TEs in the cells where they are produced. Endogenous retroviruses (ERVs), a subclass of TEs, pose a particular threat because they are capable of transiting from cell to cell. In this study, we reveal that piRNAs produced locally in germ cells counteract invasion by ERVs arriving from adjacent somatic cells. We reactivated the Drosophila ERVZAMin somatic gonadal cells by deleting, using CRISPR-Cas9 genome editing, its single copy in the somaticflamencopiRNA cluster, while keeping the piRNA pathway fully functional. Upon reactivation,ZAMinvaded the oocytes, resulting in transposition and severe fertility defects. We show that onceZAM-piRNAs are produced in germ cells they counter the invasion. Our study sheds new light on the mechanisms of recognition and regulation of invasive genetic elements, which is essential for the maintenance of genome integrity.
Project description:In metazoan gonads, transposable elements (TEs) mobilization is limited by PIWI-interacting RNAs (piRNAs). These small RNAs originate from specific source loci, the piRNA clusters. piRNAs are known to silence TEs in the cells where they are produced. Endogenous retroviruses (ERVs), a subclass of TEs, pose a particular threat because they are capable of transiting from cell to cell. In this study, we reveal that piRNAs produced locally in germ cells counteract invasion by ERVs arriving from adjacent somatic cells. We reactivated the Drosophila ERV ZAM in somatic gonadal cells by deleting, using CRISPR-Cas9 genome editing, its single copy in the somatic flamenco piRNA cluster, while keeping the piRNA pathway fully functional. Upon reactivation, ZAM invaded the oocytes, resulting in transposition and severe fertility defects. We show that once ZAM-piRNAs are produced in germ cells they counter the invasion. Our study sheds new light on the mechanisms of recognition and regulation of invasive genetic elements, which is essential for the maintenance of genome integrity.
Project description:The human genome is replete with sequences derived from foreign elements including endogenous retrovirus-like proteins of unknown function. The human genome is replete with sequences derived from foreign elements including endogenous retrovirus-like proteins of unknown function. Here we show that UBQLN2, a ubiquitin-proteasome shuttle factor implicated in neurodegenerative diseases, is regulated by the linked actions of two retrovirus-like proteins, RTL8 and PEG10. RTL8 confers on UBQLN2 the ability to complex with and regulate PEG10. PEG10, a core component of stress granules, drives the recruitment of UBQLN2 to stress granules under various stress conditions, but can only do so when RTL8 is present. Changes in PEG10 levels further remodel the kinetics of stress granule disassembly and overall composition by incorporating select extracellular vesicle proteins. Within stress granules, PEG10 forms virus-like particles, underscoring the structural heterogeneity of this class of biomolecular condensates. Together, these results reveal an unexpected link between pathways of cellular proteostasis and endogenous retrovirus-like proteins. we show that UBQLN2, a ubiquitin-proteasome shuttle factor implicated in neurodegenerative diseases, is regulated by the linked actions of two retrovirus-like proteins, RTL8 and PEG10. RTL8 confers on UBQLN2 the ability to complex with and regulate PEG10. PEG10, a core component of stress granules, drives the recruitment of UBQLN2 to stress granules under various stress conditions, but can only do so when RTL8 is present. Changes in PEG10 levels further remodel the kinetics of stress granule disassembly and overall composition by incorporating select extracellular vesicle proteins. Within stress granules, PEG10 forms virus-like particles, underscoring the structural heterogeneity of this class of biomolecular condensates. Together, these results reveal an unexpected link between pathways of cellular proteostasis and endogenous retrovirus-like proteins.
Project description:Transposable elements (TEs), whose propagation can result in severe damage to the host genome, are silenced in the animal gonad by Piwi-interacting RNAs (piRNAs). piRNAs produced in the ovaries are deposited in the embryonic germline and initiate TE repression in the germline progeny. Whether the maternally transmitted piRNAs play a role in the silencing of somatic TEs is, however, unknown. Here we show that maternally transmitted piRNAs from the tirant retrotransposon in Drosophila are required for the somatic silencing of the TE and correlate with an increase in histone H3K9 trimethylation an active tirant copy.
Project description:Transposable elements (TEs), whose propagation can result in severe damage to the host genome, are silenced in the animal gonad by Piwi-interacting RNAs (piRNAs). piRNAs produced in the ovaries are deposited in the embryonic germline and initiate TE repression in the germline progeny. Whether the maternally transmitted piRNAs play a role in the silencing of somatic TEs is, however, unknown. Here we show that maternally transmitted piRNAs from the tirant retrotransposon in Drosophila are required for the somatic silencing of the TE and correlate with an increase in histone H3K9 trimethylation an active tirant copy. Comparison of tirant piRNAs in two Drosophila simulans natural populations.
Project description:During embryonic germ cell development in mice, transposon-enriched, piwi-interacting RNAs (piRNAs) guide MILI and MIWI2 to direct silencing of potentially active mobile element families. In contrast, we know much less about the function of the highly abundant and extremely diverse class of piRNAs, which partner with MIWI and MILI during meiosis. Both MIWI and its catalytic activity are required for successful spermatogenesis, strongly indicating that piRNA-guided cleavage is critical for germ cell development. To gain an understanding of meiotic piRNA targets, we augmented the mouse piRNA repertoire by introducing an entire human meiotic piRNA cluster. This triggered a spermatogenesis defect, presumably by inappropriately targeting the piRNA machinery to mouse RNAs essential for germ cell development. Through an analysis of such de novo targets, we derived a signature for pachytene piRNA target recognition. This enabled identification of both transposable elements and meiotically expressed protein coding genes as targets of native piRNAs. Cleavage of genic targets begins at the pachytene stage when meiotic piRNAs first appear. As such, target mRNA levels attenuate starting from the pachytene stage and are further repressed throughout meiosis. Target mRNA-piRNA pairs also show evidence of an ongoing cleavage-dependent amplification cycle, which is not normally a strong feature of meiotic piRNAs. Our data support the idea that meiotic piRNA populations must be strongly selected to enable successful spermatogenesis, both driving the response away from essential genes and directing the pathway toward mRNA targets that are regulated by small RNAs in meiotic cells. 48 samples