piRNA-mediated regulation of transposon alternative splicing in the soma and germ line

Teixeira, Felipe Karam; Okuniewska, Martyna; Malone, Colin D.; Coux, Remi-Xavier; Rio, Donald C.; Lehmann, Ruth

doi:10.1038/nature25018

Cited by 113 publications

(119 citation statements)

References 55 publications

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“…This is indeed the strategy taken by a DNA transposon, P-element (Teixeira et al, 2017). However, our data indicate that retrotransposons do not mobilize prior to differentiation.…”

Section: Resultsmentioning

confidence: 99%

Hijacking Oogenesis Enables Massive Propagation of LINE and Retroviral Transposons

Wang

Dou

Moon

et al. 2018

Cell

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Although animals have evolved multiple mechanisms to suppress transposons, "leaky" mobilizations that cause mutations and diseases still occur. This suggests that transposons employ specific tactics to accomplish robust propagation. By directly tracking mobilization, we show that, during a short and specific time window of oogenesis, retrotransposons achieve massive amplification via a cell-type-specific targeting strategy. Retrotransposons rarely mobilize in undifferentiated germline stem cells. However, as oogenesis proceeds, they utilize supporting nurse cells-which are highly polyploid and eventually undergo apoptosis-as factories to massively manufacture invading products. Moreover, retrotransposons rarely integrate into nurse cells themselves but, instead, via microtubule-mediated transport, they preferentially target the DNA of the interconnected oocytes. Blocking microtubule-dependent intercellular transport from nurse cells significantly alleviates damage to the oocyte genome. Our data reveal that parasitic genomic elements can efficiently hijack a host developmental process to propagate robustly, thereby driving evolutionary change and causing disease.

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“…This is indeed the strategy taken by a DNA transposon, P-element (Teixeira et al, 2017). However, our data indicate that retrotransposons do not mobilize prior to differentiation.…”

Section: Resultsmentioning

confidence: 99%

Hijacking Oogenesis Enables Massive Propagation of LINE and Retroviral Transposons

Wang

Dou

Moon

et al. 2018

Cell

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“…RNAseq data from heat-stressed plants were obtained from (Pietzenuk et al 2016) and analyzed as described above. Splicing of intronic TE insertions was calculated as described previously (Teixeira et al 2017). Briefly, the number of split-reads (SR) and non-splitreads (NSR, which should be fully and uniquely contained within the interval surrounding the same exon-intron junction) mapping to an exon-intron junction was extracted and the ratio SR/(SR+NSR)*100 was then calculated.…”

Section: Author Contributionsmentioning

confidence: 99%

Transposon accumulation lines uncover histone H2A.Z-driven integration bias towards environmentally responsive genes

Quadrana

Etcheverry

Gilly

et al. 2018

Preprint

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Inherited transposition events are important drivers of genome evolution but because transposable element (TE) mobilization is usually rare, its impact on the creation of genetic variation remains poorly characterized. Here, we used a population of A. thaliana epigenetic recombinant inbred lines (epiRILs) to characterize >8000 de novo insertions produced by several TEs families also active in nature. Integration was strongly biased towards genes, with evident deleterious effects. Biases were TE family-specific and associated with distinct chromatin features. Notably, we demonstrate that the histone variant H2A.Z guides the preferential integration of Ty1/Copia LTR-retrotransposons within environmentally responsive genes and that this guiding function is evolutionary conserved. Finally, we uncover an important role for epigenetic silencing in exacerbating or alleviating the effects of TE insertions on target genes. These findings establish chromatin as a major determinant of the spectrum and functional impact of TE-generated mutations, with important implications for adaptation and evolution. VC, PW and JMA conceived the project, with substantial additional input from LQ. ME and EC performed DNA and RNA extraction; JG, SE and JMA produced the WGS data; AG, ME, JMA and LQ performed the detection of TE insertions in the epiRILs; VB identified excision footprints in the epiRILs. LQ performed all of the other bioinformatic analyses, as well as the TE sequence capture and RT-

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“…As Argonaute recruitment requires the nascent target RNA, this process is defined as 'co-transcriptional silencing'. Besides impacting chromatin and transcription, nuclear small RNA pathways have also been linked to the co-transcriptional processes of splicing, RNA quality control and turnover (Dumesic et al, 2013;Reyes-Turcu et al, 2011;Teixeira et al, 2017). Together, this hints at complex molecular connections between nuclear Argonautes, the nascent target RNA, and chromatin.…”

Section: Introductionmentioning

confidence: 99%

The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation

Batki

Schnabl

Wang

et al. 2019

Preprint

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The PIWI-interacting RNA (piRNA) pathway protects animal genome integrity in part through establishing repressive heterochromatin at transposon loci. Silencing requires piRNA-guided targeting of nuclear PIWI proteins to nascent transposon transcripts, yet the subsequent molecular events are not understood. Here, we identify SFiNX (Silencing Factor interacting Nuclear eXport variant), an interdependent protein complex required for Piwimediated co-transcriptional silencing in Drosophila. SFiNX consists of Nxf2-Nxt1, a gonadspecific variant of the heterodimeric mRNA export receptor Nxf1-Nxt1, and the Piwiassociated protein Panoramix. SFiNX mutant flies are sterile and exhibit transposon derepression because piRNA-loaded Piwi is unable to establish heterochromatin. Within SFiNX, Panoramix recruits the heterochromatin effectors, while the RNA binding Nxf2 protein licenses co-transcriptional silencing. Our data reveal how Nxf2 evolved from an RNA transport receptor into a co-transcriptional silencing factor. Thus, NXF-variants, which are abundant in metazoans, can have diverse molecular functions and might have been co-opted for host genome defense more broadly.Please note: In the first version of this bioRxiv preprint, we reported CLIP-seq data for Nxf2. In the meantime, we found an unexpected de-repression of gypsy (but not mdg1) transposons in the Cas9-engineered Nxf2-GFP line. We therefore do not trust the CLIP-seq data anymore and removed it from this updated submission. We apologize for any confusion that might have been caused by this.Batki, Schnabl, Wang et al. April 28, 2019 |The PIWI-interacting RNA (piRNA) pathway protects animal genome integrity in part through establishing repressive heterochromatin at transposon loci. Silencing requires piRNAguided targeting of nuclear PIWI proteins to nascent transposon transcripts, yet the subsequent molecular events are not understood. Here, we identify SFiNX (Silencing Factor interacting Nuclear eXport variant), an interdependent protein complex required for Piwi-mediated co-transcriptional silencing in Drosophila. SFiNX consists of Nxf2-Nxt1, a gonadspecific variant of the heterodimeric mRNA export receptor Nxf1-Nxt1, and the Piwi-associated protein Panoramix. SFiNX mutant flies are sterile and exhibit transposon de-repression because piRNA-loaded Piwi is unable to establish heterochromatin. Within SFiNX, Panoramix recruits the heterochromatin effectors, while the RNA binding Nxf2 protein licenses co-transcriptional silencing. Our data reveal how Nxf2 evolved from an RNA transport receptor into a cotranscriptional silencing factor. Thus, NXF-variants, which are abundant in metazoans, can have diverse molecular functions and might have been co-opted for host genome defense more broadly.

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piRNA-mediated regulation of transposon alternative splicing in the soma and germ line

Cited by 113 publications

References 55 publications

Hijacking Oogenesis Enables Massive Propagation of LINE and Retroviral Transposons

Hijacking Oogenesis Enables Massive Propagation of LINE and Retroviral Transposons

Transposon accumulation lines uncover histone H2A.Z-driven integration bias towards environmentally responsive genes

The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation

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