Key role of piRNAs in telomeric chromatin maintenance and telomere nuclear positioning in<i>Drosophila</i>germline

Radion, Elizaveta; Morgunova, Valeriya; Ryazansky, Sergei; Akulenko, Natalia; Lavrov, Sergey; Abramov, Yuri; Olovnikov, Ivan; Kalmykova, Alla

doi:10.1101/163030

Cited by 7 publications

(14 citation statements)

References 75 publications

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“…Our observation that telomeres are longer in strains with terminal deficiencies suggests that subtelomeric sequences also regulate telomere elongation, consistent with previous studies [72][73][74].…”

Section: Host Regulation Of the Httssupporting

confidence: 92%

Rapid evolution at the Drosophila telomere: transposable element dynamics at an intrinsically unstable locus

McGurk

Dion-Côté

Barbash

2019

Preprint

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Background: Drosophila telomeres have been maintained by three families of active transposable elements (TEs), HeT-A, TAHRE and TART, collectively referred to as HTTs, for tens of millions of years.The conservation of this arrangement contrasts with an unusually high degree of HTT interspecific variation. While the impacts of conflict and domestication are often invoked to explain HTT variation, the telomeres are unstable structures such that neutral mutational processes and evolutionary tradeoffs may also drive HTT evolution. Results:We leveraged population genomic data to analyze nearly 10,000 HTT insertions in 85 D.melanogaster genomes and compared their variation to TE families evolving under more typical dynamics. We find that distinct aspects of HTT copy number variation and sequence diversity largely reflect telomere instability, with HTT insertions being lost at much higher rates than other TEs elsewhere in the genome. However, occasional copy number expansions of both HTTs and other TE families occur, highlighting that the HTTs are, like their feral cousins, typically repressed but primed to take over given the opportunity. We further find that some HTT families may be activated by the erosion of whole telomeres, suggesting the existence of HTT-specific host control mechanisms. Conclusions:Even the persistent telomere localization of HTTs may not reflect domestication, but rather a highly successful evolutionary strategy to reduce their impact on the host genome. We propose that HTT evolution is driven by multiple processes including domestication, genetic conflict, niche specialization, and telomere instability, with the latter two being previously underappreciated and likely predominant.

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Section: Host Regulation Of the Httssupporting

confidence: 92%

Rapid evolution at the Drosophila telomere: transposable element dynamics at an intrinsically unstable locus

McGurk

Dion-Côté

Barbash

2019

Preprint

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“…Interestingly, we found that Het-A chromatin left nuclear peripheries upon loss of either Panx or dNxf2 (Extended Data Fig. 10) 20 . Transposon transcripts (I element) which are targeted by piRNAs have been previously shown to accumulate within nucleus 21 .…”

Section: Figurementioning

confidence: 79%

“… a , Density plots for dNxf2-Halo GoldCLIP reads from Mael knockdown OSCs (top panel), dNxf2-Halo GoldCLIP reads from LacZ knockdown OSCs (middle panel), and Panx co-immunoprecipitated smRNA reads (bottom panel, from previously published data 20 ) over the transposon consensus of mdg1. b and c are the same as in a except for gypsy ( b ) and 297 ( c ).…”

Section: Materials and Correspondencementioning

confidence: 99%

A Pandas complex adapted for piRNA-guided transposon silencing

Zhao

Cheng

Miao

et al. 2019

Preprint

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40The repression of transposons by the Piwi-interacting RNA (piRNA) pathway is essential to 41 protect animal germ cells. In Drosophila ovaries, Panoramix (Panx) enforces transcriptional 42 silencing by binding to the target-engaged Piwi-piRNA complex, although the precise 43 mechanisms by which this occur remain elusive. Here, we show that Panx functions 44 together with a germline specific paralogue of a nuclear export factor, dNxf2, and its 45 cofactor dNxt1 (p15) as a ternary complex to suppress transposon expression. Structural 46 and functional analysis demonstrate that dNxf2 binds Panx via its UBA domain and play an 47 important role in transposon silencing through binding to transposon transcripts directly. 48Unexpectedly, dNxf2 interacts directly with dNxf1 (TAP), which is also essential for 49 transposon silencing. Transient tethering of dNxf2 to nascent transcripts leads to their 50 nuclear retention. Therefore, we propose that dNxf2 may function as a Pandas (Panoramix-51 dNxf2 dependent TAP/p15 silencing) complex, which counteracts the canonical RNA 52 exporting machinery (TAP/p15) and restricts transposons to nuclear peripheries. Our 53 findings may have broader implications for understanding how RNA metabolism modulates 54 epigenetic gene silencing and heterochromatin formation. 55 56Transposons are highly abundant in eukaryotes, which make up nearly half of human genome. To 57 maintain eukaryotic genome integrity, nascent transcripts of transposons are often targeted by 58 nuclear Argonaute proteins for transcriptional gene silencing (TGS) 1-5 . In animal gonads, the PIWI-59 clade Argonautes guided by piRNAs (PIWI-interacting RNA) are thought to recognize nascent 60 transposon transcripts and direct sequence-specific heterochromatin formation 3 . As a critical 61 cofactor of Drosophila nuclear Piwi, Panoramix (Panx, also known as Silencio) links the target-62 engaged Piwi-piRNA complex to the general silencing machinery 6,7 . Enforced tethering of Panx to 63 nascent transcripts leads to cotranscriptional silencing and correlates with deposition of histone H3 64 lysine 9 trimethylation (H3K9me3) marks 6,7 . However, the mechanism by which Panx mediates the 65 repression remains unknown. An equally important question is why H3K9me3 marks are not always 66 sufficient for transposon silencing 8 . 67 68To understand this fundamental question, we cross-examined proteins that co-69 immunoprecipitated with Panx (Extended Data Fig. 1a) with piRNA pathway candidate genes from 70 RNA interference (RNAi) screens 9-12 . Unexpectedly, dNxf2 was identified as a potential cofactor of 71 Panx (Extended Data Fig.1a-c). dNxf2 belongs to an evolutionarily conserved NXF (nuclear export 72 factor) family of proteins, yet depletion of dNxf2 had no effect on polyadenylated mRNA export 13,14 . 73Instead, dNxf2 and its cofactor dNxt1 (also known as p15) were both identified in two published 74RNAi screens as being essential for transposon silencing 9,10 . Similar to Panx, dNxf2 is specifically 75 expressed in female gonads...

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“…As mentioned above, Het-A, TART and TAHRE produce both sense and antisense transcripts [45,50,51]. Although Het-A and TART share common genomic niche, these elements exhibit also specific genetic requirements for their silencing and regulation [44,49,[91][92][93][94].…”

Section: Regulation Of Telomeric Transposition In the Germline: Piwi mentioning

confidence: 93%

“…piRNAs originate from genomic loci named 'piRNA clusters' [106]. HTT arrays represent specialized piRNA clusters, whose transcripts are both the piRNA precursors and their unique targets [91]. piRNA producing loci are characterized by a peculiar chromatin organization, enriched in H3K9me3 bound by the RDC complex formed by Rhino (Rhi, a paralogue of the heterochromatic protein HP1), Deadlock (Del), and Cutoff (Cuff) [107].…”

Section: Regulation Of Telomeric Transposition In the Germline: Piwi mentioning

confidence: 99%

Silence at the End: How Drosophila Regulates Expression and Transposition of Telomeric Retroelements

Cacchione

Cenci

Raffa

2020

Journal of Molecular Biology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Key role of piRNAs in telomeric chromatin maintenance and telomere nuclear positioning inDrosophilagermline

Cited by 7 publications

References 75 publications

Rapid evolution at the Drosophila telomere: transposable element dynamics at an intrinsically unstable locus

Rapid evolution at the Drosophila telomere: transposable element dynamics at an intrinsically unstable locus

A Pandas complex adapted for piRNA-guided transposon silencing

Silence at the End: How Drosophila Regulates Expression and Transposition of Telomeric Retroelements

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