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Modulation of Aub-TDRD interactions elucidates piRNA amplification and germplasm formation.

ABSTRACT: Aub guided by piRNAs ensures genome integrity by cleaving retrotransposons, and genome propagation by trapping mRNAs to form the germplasm that instructs germ cell formation. Arginines at the N-terminus of Aub (Aub-NTRs) interact with Tudor and other Tudor domain-containing proteins (TDRDs). Aub-TDRD interactions suppress active retrotransposons via piRNA amplification and form germplasm via generation of Aub-Tudor ribonucleoproteins. Here, we show that Aub-NTRs are dispensable for primary piRNA biogenesis but essential for piRNA amplification and that their symmetric dimethylation is required for germplasm formation and germ cell specification but largely redundant for piRNA amplification.

SUBMITTER: Vrettos N

PROVIDER: S-EPMC7772777 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Modulation of Aub-TDRD interactions elucidates piRNA amplification and germplasm formation.

Vrettos Nicholas N Maragkakis Manolis M Alexiou Panagiotis P Sgourdou Paraskevi P Ibrahim Fadia F Palmieri Daniel D Kirino Yohei Y Mourelatos Zissimos Z

Life science alliance 20201229 3

Aub guided by piRNAs ensures genome integrity by cleaving retrotransposons, and genome propagation by trapping mRNAs to form the germplasm that instructs germ cell formation. Arginines at the N-terminus of Aub (Aub-NTRs) interact with Tudor and other Tudor domain-containing proteins (TDRDs). Aub-TDRD interactions suppress active retrotransposons via piRNA amplification and form germplasm via generation of Aub-Tudor ribonucleoproteins. Here, we show that Aub-NTRs are dispensable for primary piRNA ...[more]

PMID: 33376130

Similar Datasets

Modulation of Aub–Tdrd interactions elucidates piRNA amplification and germ plasm formation

Project description:Aub protein guided by piRNAs ensures genome integrity by cleaving retrotransposons and genome propagation by trapping mRNAs to form the germ plasm that instructs germ cell formation. The amino terminus of Aub (Aub-NT) is rich in arginines (Aub-NTRs), which are symmetrically dimethylated (sDMAs), and interacts with Tudor protein and other Tudor domain containing proteins (Tdrds). Aub-Tdrd interactions play critical roles in suppressing active retrotransposons via piRNA amplification and in germ plasm formation via generation of Aub-Tudor ribonucleoproteins. Here we show that Aub-NTRs are dispensable for primary piRNA biogenesis but essential for piRNA amplification and transposon control and that sDMAs in Aub-NT are essential for germ plasm formation and germ cell specification, but largely dispensable for piRNA amplification and transposon control.

2020-12-14 | GSE155874 | GEO

Modulation of Aub–Tdrd interactions elucidates piRNA amplification and germ plasm formation

Project description:Modulation of Aub–Tdrd interactions elucidates piRNA amplification and germ plasm formation

| PRJNA655907 | ENA

Binding of guide piRNA triggers methylation of the unstructured N-terminal region of Aub leading to assembly of the piRNA amplification complex.

Project description:PIWI proteins use guide piRNAs to repress selfish genomic elements, protecting the genomic integrity of gametes and ensuring the fertility of animal species. Efficient transposon repression depends on amplification of piRNA guides in the ping-pong cycle, which in Drosophila entails tight cooperation between two PIWI proteins, Aub and Ago3. Here we show that post-translational modification, symmetric dimethylarginine (sDMA), of Aub is essential for piRNA biogenesis, transposon silencing and fertility. Methylation is triggered by loading of a piRNA guide into Aub, which exposes its unstructured N-terminal region to the PRMT5 methylosome complex. Thus, sDMA modification is a signal that Aub is loaded with piRNA guide. Amplification of piRNA in the ping-pong cycle requires assembly of a tertiary complex scaffolded by Krimper, which simultaneously binds the N-terminal regions of Aub and Ago3. To promote generation of new piRNA, Krimper uses its two Tudor domains to bind Aub and Ago3 in opposite modification and piRNA-loading states. Our results reveal that post-translational modifications in unstructured regions of PIWI proteins and their binding by Tudor domains that are capable of discriminating between modification states is essential for piRNA biogenesis and silencing.

| S-EPMC8249470 | biostudies-literature

Binding of guide piRNA triggers methylation of the unstructured N-terminal region of Aub leading to assembly of the piRNA amplification complex

Project description:In Drosophila, Piwi proteins use guide piRNAs to repress selfish genomic elements, protecting the genomic integrity of gametes and ensuring the fertility of animal species. Efficient transposon repression depends on amplification of piRNA guides in the ping-pong cycle, which in Drosophila entails tight cooperation between two Piwi proteins, Aub and Ago3. Here we show that post-translational modification, symmetric dimethylarginine (sDMA), of Aub is essential for piRNA biogenesis, transposon silencing and fertility. Methylation is triggered by loading of a piRNA guide into Aub, which exposes its unstructured N-terminal region to the PRMT5 methylosome complex. Thus, sDMA modification is a signal that Aub is loaded with piRNA guide. Amplification of piRNA in the ping-pong cycle requires assembly of a tertiary complex scaffolded by Krimper, which simultaneously binds the N-terminal regions of Aub and Ago3. To promote generation of new piRNA, Krimp uses its two Tudor domains to bind Aub and Ago3 in opposite modification and piRNA-loading states. Our results reveal essential functions of post-translational modifications in unstructured regions of Piwi proteins and of Tudor domains capable of discriminating between modification states in piRNA biogenesis and silencing.

2020-06-25 | GSE153156 | GEO

Slicing and Binding by Ago3 or Aub Trigger Piwi-Bound piRNA Production by Distinct Mechanisms.

Project description:In Drosophila ovarian germ cells, PIWI-interacting RNAs (piRNAs) direct Aubergine and Argonaute3 to cleave transposon transcripts and instruct Piwi to repress transposon transcription, thereby safeguarding the germline genome. Here, we report that RNA cleavage by Argonaute3 initiates production of most Piwi-bound piRNAs. We find that the cardinal function of Argonaute3, whose piRNA guides predominantly correspond to sense transposon sequences, is to produce antisense piRNAs that direct transcriptional silencing by Piwi, rather than to make piRNAs that guide post-transcriptional silencing by Aubergine. We also find that the Tudor domain protein Qin prevents Aubergine's cleavage products from becoming Piwi-bound piRNAs, ensuring that antisense piRNAs guide Piwi. Although Argonaute3 slicing is required to efficiently trigger phased piRNA production, an alternative, slicing-independent pathway suffices to generate Piwi-bound piRNAs that repress transcription of a subset of transposon families. This alternative pathway may help flies silence newly acquired transposons for which they lack extensively complementary piRNAs.

| S-EPMC4560842 | biostudies-literature

Ribosomes guide pachytene piRNA formation on long intergenic piRNA precursors.

Project description:PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs essential for fertility. In adult mouse testes, most piRNAs are derived from long single-stranded RNAs lacking annotated open reading frames (ORFs). The mechanisms underlying how piRNA sequences are defined during the cleavages of piRNA precursors remain elusive. Here, we show that 80S ribosomes translate the 5'-proximal short ORFs (uORFs) of piRNA precursors. The MOV10L1/Armitage RNA helicase then facilitates the translocation of ribosomes into the uORF downstream regions (UDRs). The ribosome-bound UDRs are targeted by piRNA processing machinery, with the processed ribosome-protected regions becoming piRNAs. The dual modes of interaction between ribosomes and piRNA precursors underlie the distinct piRNA biogenesis requirements at uORFs and UDRs. Ribosomes also mediate piRNA processing in roosters and green lizards, implying that this mechanism is evolutionarily conserved in amniotes. Our results uncover a function for ribosomes on non-coding regions of RNAs and reveal the mechanisms underlying how piRNAs are defined.

| S-EPMC8041231 | biostudies-literature

The interplay between the Argonaute proteins Piwi and Aub within Drosophila germarium is critical for oogenesis, piRNA biogenesis and TE silencing.

Project description:Transposable elements (TEs) have invaded most genomes and constitute up to 50% of the human genome. Machinery based on small non-coding piRNAs has evolved to inhibit their expression at the transcriptional and post-transcriptional levels. Surprisingly, this machinery is weakened during specific windows of time in mice, flies or plants, allowing the expression of TEs in germline cells. The function of this de-repression remains unknown. In Drosophila, we have previously shown that this developmental window is characterized by a reduction of Piwi expression in dividing germ cells. Here, we show that the unique knock-down of Aub in these cells leads to female sterility. It correlates with defects in piRNA amplification, an increased Piwi expression and an increased silencing of transcriptionally silenced TEs. These defects are similar to those observed when Aub is depleted in the whole germline which underlies the crucial role of this developmental window for both oogenesis and TE silencing. We further show that, with age, some fertility is recovered which is concomitant to a decrease of Piwi and TE silencing. These data pinpoint the Pilp as a tremendously important step for female fertility and genome stability. They further show that such a restricted developmental niche of germ cells may sense environmental changes, such as aging, to protect the germline all along the life.

| S-EPMC6212714 | biostudies-literature

The RNA-Binding ATPase, Armitage, Couples piRNA Amplification in Nuage to Phased piRNA Production on Mitochondria.

Project description:PIWI-interacting RNAs (piRNAs) silence transposons in Drosophila ovaries, ensuring female fertility. Two coupled pathways generate germline piRNAs: the ping-pong cycle, in which the PIWI proteins Aubergine and Ago3 increase the abundance of pre-existing piRNAs, and the phased piRNA pathway, which generates strings of tail-to-head piRNAs, one after another. Proteins acting in the ping-pong cycle localize to nuage, whereas phased piRNA production requires Zucchini, an endonuclease on the mitochondrial surface. Here, we report that Armitage (Armi), an RNA-binding ATPase localized to both nuage and mitochondria, links the ping-pong cycle to the phased piRNA pathway. Mutations that block phased piRNA production deplete Armi from nuage. Armi ATPase mutants cannot support phased piRNA production and inappropriately bind mRNA instead of piRNA precursors. We propose that Armi shuttles between nuage and mitochondria, feeding precursor piRNAs generated by Ago3 cleavage into the Zucchini-dependent production of Aubergine- and Piwi-bound piRNAs on the mitochondrial surface.

| S-EPMC6636356 | biostudies-literature

Antisense piRNA amplification, but not piRNA production or nuage assembly, requires the Tudor-domain protein Qin.

Project description: Not available

| S-EPMC3989648 | biostudies-literature

piRNA production requires heterochromatin formation in Drosophila.

Project description:Protecting the genome from transposable element (TE) mobilization is critical for germline development. In Drosophila, Piwi proteins and their bound small RNAs (piRNAs) provide a potent defense against TE activity. TE targeting piRNAs are processed from TE-dense heterochromatic loci termed piRNA clusters. Although piRNA biogenesis from cluster precursors is beginning to be understood, little is known about piRNA cluster transcriptional regulation. Here, we show that deposition of histone 3 lysine 9 by the methyltransferase dSETDB1 (egg) is required for piRNA cluster transcription. In the absence of dSETDB1, cluster precursor transcription collapses in germline and somatic gonadal cells and TEs are activated, resulting in germline loss and a block in germline stem cell differentiation. We propose that heterochromatin protects the germline by activating the piRNA pathway.

| S-EPMC3205116 | biostudies-literature

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