tRNA processing defects induce replication stress and Chk2‐dependent disruption of piRNA transcription

Mollà-Herman, Anahi; Vallés, Ana María; Ganem‐Elbaz, Carine; Antoniewski, Christophe; Huynh, Jean‐René

doi:10.15252/embj.201591006

Cited by 57 publications

(71 citation statements)

References 97 publications

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“…Additionally, we observed the highest frequency of 1U containing piRNAs among all repeat derived piRNAs across all length ( Supporting Information, Fig. 50 We also hypothesize a similar phenomenon operating here upon visualizing the vast majority of piRNAs mapped to tRNAs of Gly, Val, Lys, Asn, and Met ( Figure 5). It is believed that the intermediate piRNA fragments with above said nucleotide bias are preferably bound by PIWI proteins which could be due to the presence of 5 0 binding pocket that has steric preference for such piRNAs, thus creating bias with 1U at 5 0 termini.…”

Section: Pirnas Derived From Transposable Elementssupporting

confidence: 70%

Investigating piwi‐interacting RNA regulome in human neuroblastoma

Roy

Mallick

2018

Genes Chromosomes & Cancer

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Remarkable attempts have been exercised in recent years using high-throughput technologies to identify and decipher the functions of piRNAs in various abnormalities like cancer. However, piRNAs in the oncogenesis of neuroblastoma (NB) has not been reported yet even after their illustrated roles in neurological processes. Therefore, we investigated the piRNA transcriptome in IMR-32 and SH-SY-5Y NB cell lines by employing high-throughput next-generation sequencing after confirming the expression of three associated PIWILs both at mRNAs and protein level by qRT-PCR and immunofluroscence, respectively. We identified a common pool of 525 piRNAs of 26-32 nts long expressed in both the cell lines. The possible functions of these piRNAs were charted by predicting their targeting on retrotransposon-containing 1769 mRNAs differentially expressed in 39 NB cell lines followed by network and pathway analysis. The analysis revealed that majority of the target binding sites in NB fall within retrotransposons residing within the 3'UTR of target mRNA transcripts like miRNA-targets. Further, we validated the expression of key piRNAs and their target genes enriched in cancer-related networks, pathways and biological processes which are hypothesized to play crucial roles in neoplastic events of NB. We believe that the evidence of piRNAs in human NB and their possible contribution to its pathogenesis reported in this work will open up new exciting possibilities for piRNA-mediated therapeutics for this malignancy.

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Section: Pirnas Derived From Transposable Elementssupporting

confidence: 70%

Investigating piwi‐interacting RNA regulome in human neuroblastoma

Roy

Mallick

2018

Genes Chromosomes & Cancer

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“…This has been shown to be tightly connected with the piRNA pathway: For instance, expression of piRNA clusters depends (directly or indirectly) on methylation marks (Rangan et al 2011; Goriaux et al 2014; Mohn et al 2014; Molla-Herman et al 2015), and piRNA-mediated transcriptional silencing triggers the deposition of repressive H3K9me3 marks. Other mechanisms—such as endo-siRNAs and miRNAs—are also able to recruit this silencing machinery leading to heterochromatin formation (Holoch and Moazed 2015).…”

Section: Discussionmentioning

confidence: 99%

Transposable Element Misregulation Is Linked to the Divergence between Parental piRNA Pathways in Drosophila Hybrids

Romero‐Soriano

Modolo

Lopez-Maestre

et al. 2017

Genome Biology and Evolution

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Interspecific hybridization is a genomic stress condition that leads to the activation of transposable elements (TEs) in both animals and plants. In hybrids between Drosophila buzzatii and Drosophila koepferae, mobilization of at least 28 TEs has been described. However, the molecular mechanisms underlying this TE release remain poorly understood. To give insight on the causes of this TE activation, we performed a TE transcriptomic analysis in ovaries (notorious for playing a major role in TE silencing) of parental species and their F1 and backcrossed (BC) hybrids. We find that 15.2% and 10.6% of the expressed TEs are deregulated in F1 and BC1 ovaries, respectively, with a bias toward overexpression in both cases. Although differences between parental piRNA (Piwi-interacting RNA) populations explain only partially these results, we demonstrate that piRNA pathway proteins have divergent sequences and are differentially expressed between parental species. Thus, a functional divergence of the piRNA pathway between parental species, together with some differences between their piRNA pools, might be at the origin of hybrid instabilities and ultimately cause TE misregulation in ovaries. These analyses were complemented with the study of F1 testes, where TEs tend to be less expressed than in D. buzzatii. This can be explained by an increase in piRNA production, which probably acts as a defence mechanism against TE instability in the male germline. Hence, we describe a differential impact of interspecific hybridization in testes and ovaries, which reveals that TE expression and regulation are sex-biased.

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“…Most recently, individual paternal 5′ tRFs have been implicated in apparent downregulation of a small group of LTR-associated genes in mouse by an unknown mechanism (Sharma et al, 2016), and in targeting of some Gypsy elements in Arabidopsis by partial complementarity to various regions (Martinez et al, 2017). Finally, 5′ tRNA processing in Drosophila affects the expression of neighboring piRNA clusters and their DNA- and RNA-transposon targets (Molla-Herman et al, 2015). Little is known about the biological functions of 3′ tRFs.…”

Section: Introductionmentioning

confidence: 99%

LTR-Retrotransposon Control by tRNA-Derived Small RNAs

Schorn

Gutbrod

LeBlanc

et al. 2017

Cell

326

345

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SUMMARY Transposon reactivation is an inherent danger in cells that lose epigenetic silencing during developmental reprogramming. In the mouse, LTR-retrotransposons, or endogenous retroviruses (ERV), account for most novel insertions and are expressed in the absence of histone H3 Lysine 9 trimethylation in preimplantation stem cells. We found abundant, 18 nt tRNA-derived small RNA (tRF) in these cells, and ubiquitously expressed 22 nt tRFs, that include the 3′ terminal CCA of mature tRNAs, and target the tRNA primer binding site (PBS) essential for ERV reverse transcription. We show that the two most active ERV families, IAP and MusD/ETn, are major targets and are strongly inhibited by tRFs in retrotransposition assays. 22 nt tRFs post-transcriptionally silence coding-competent ERVs, while 18 nt tRFs specifically interfere with reverse transcription and retrotransposon mobility. The PBS offers a unique target to specifically inhibit LTR-retrotransposons and tRF-targeting is a potentially highly conserved mechanism of small RNA-mediated transposon control.

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tRNA processing defects induce replication stress and Chk2‐dependent disruption of piRNA transcription

Cited by 57 publications

References 97 publications

Investigating piwi‐interacting RNA regulome in human neuroblastoma

Investigating piwi‐interacting RNA regulome in human neuroblastoma

Transposable Element Misregulation Is Linked to the Divergence between Parental piRNA Pathways in Drosophila Hybrids

LTR-Retrotransposon Control by tRNA-Derived Small RNAs

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