Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi

Chen, Chen; Jin, Jing; Adams-Cioaba, Melanie A.; Park, Jin Gyoon; Guo, Yahong; Tenaglia, Enrico; Xu, Chao; Gish, Gerald; Min, Jinrong; Pawson, Tony

doi:10.1073/pnas.0911640106

Cited by 166 publications

(183 citation statements)

References 35 publications

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“…S1). We and others have also found MOV10L1 in immunoprecipitated MILI, MIWI, and MIWI2 complexes by mass spectrometry (15,16). Consistent with the mass spectrometry data, coimmunoprecipitations followed by Western blot analysis showed abundant association of MOV10L1 with MILI but less with TDRD1 and MIWI ( Fig.…”

Section: Mov10l1supporting

confidence: 68%

Mouse MOV10L1 associates with Piwi proteins and is an essential component of the Piwi-interacting RNA (piRNA) pathway

Zheng

Xiol

Reuter

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

203

265

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Piwi-interacting RNAs (piRNAs) are essential for silencing of transposable elements in the germline, but their biogenesis is poorly understood. Here we demonstrate that MOV10L1, a germ cell-specific putative RNA helicase, is associated with Piwi proteins. Genetic disruption of the MOV10L1 RNA helicase domain in mice renders both MILI and MIWI2 devoid of piRNAs. Absence of a functional piRNA pathway in Mov10l1 mutant testes causes loss of DNA methylation and subsequent derepression of retrotransposons in germ cells. The Mov10l1 mutant males are sterile owing to complete meiotic arrest. This mouse mutant expresses Piwi proteins but lacks piRNAs, suggesting that MOV10L1 is required for piRNA biogenesis and/or loading to Piwi proteins.T he Piwi clade of Argonaute proteins associates with a class of 26-31-nt germline-specific small RNAs called "piRNAs". Together they participate in suppression of transposable elements in all animals studied (1-4). In mice, the Piwi clade contains three members: Miwi2, Mili, and Miwi. These three Piwi members exhibit distinct developmental expression patterns. Miwi2 is expressed in perinatal male germ cells (5), whereas Mili is more broadly expressed from embryonic germ cells to postnatal round spermatids (6). Miwi expression begins in pachytene spermatocytes and persists in haploid round spermatids (7). The overlapping temporal expression of Mili with Miwi and Miwi2 points to the pivotal role of MILI in the piRNA pathway, as further supported by the fact that MILI is associated with developmental stage-dependent pools of piRNAs: prenatal, prepachytene, and pachytene piRNAs (5,8,9).The mechanisms of piRNA biogenesis are largely unclear (1-4). One feature of piRNAs in all species is their highly clustered genomic origins. Several of these clusters produce piRNAs only from one strand. This leads to a hypothesized primary processing pathway whereby an unknown nuclease cleaves off mature piRNAs from a long single-stranded precursor transcript. On the other hand, some piRNAs in prenatal and prepachytene pools display signatures indicative of a proposed RNA-mediated amplification loop that uses primary piRNAs to generate secondary piRNAs from precursor transcripts (ping-pong mechanism) (10, 11). Apart from the Piwi proteins themselves, factors directly impacting piRNA production are unknown.We previously identified Mov10l1 as a gene specifically expressed in mouse germ cells, which encodes a putative RNA helicase of unknown function (12). Whereas the N-terminal half of MOV10L1 is not homologous to any other mouse proteins, its C-terminal RNA helicase domain exhibits low homology (45% amino acid identity) with MOV10. MOV10, the vertebrate homolog of Drosophila Armi, is ubiquitously expressed. In mammalian cells, MOV10 is associated with Argonaute proteins in the RNA-induced silencing complex (RISC) and is functionally required for RNA interference (13, 14). Here we demonstrate that MOV10L1 is an essential factor in the piRNA pathway. Results MOV10L1 Is Associated with Piwi Proteins.To identi...

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Section: Mov10l1supporting

confidence: 68%

Mouse MOV10L1 associates with Piwi proteins and is an essential component of the Piwi-interacting RNA (piRNA) pathway

Zheng

Xiol

Reuter

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

203

265

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“…In addition, some tudor domains recognize methylated arginine residues of histone and nonhistone proteins (16)(17)(18)(19)(20). These methylation-dependent interactions impact a wide spectrum of biological processes in eukaryotes.…”

Section: Discussionmentioning

confidence: 99%

Distinct mode of methylated lysine-4 of histone H3 recognition by tandem tudor-like domains of Spindlin1

Yang

Wang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Recognition of methylated histone tail lysine residues by tudor domains plays important roles in epigenetic control of gene expression and DNA damage response. Previous studies revealed the binding of methyllysine in a cage of aromatic residues, but the molecular mechanism by which the sequence specificity for surrounding histone tail residues is achieved remains poorly understood. In the crystal structure of a trimethylated histone H3 lysine 4 (H3K4) peptide bound to the tudor-like domains of Spindlin1 presented here, an atypical mode of methyllysine recognition by an aromatic pocket of Spindlin1 is observed. Furthermore, the histone sequence is recognized in a distinct manner involving the amino terminus and a pair of arginine residues of histone H3, and disruption of the binding impaired stimulation of pre-RNA expression by Spindlin1. Our analysis demonstrates considerable diversities of methyllysine recognition and sequence-specific binding of histone tails by tudor domains, and the revelation furthers the understanding of tudor domain proteins in deciphering epigenetic marks on histone tails.H istone lysine methylation imparts epigenetic information in chromatin biology, and the transduction of epigenetic signal is mediated by a diverse group of proteins containing methyllysine recognition domains (1). Some of the best known methyllysine recognition modules include chromo, tudor, MBT (Malignant Brain Tumor), and PHD (Plant Homeodomain) domains (2-4). A recent addition of this family of histone methyllysine "readers" is the BAH domain ORC1 (5). These methyllysine "readers" can recognize histone lysine methylation in a site-specific and methylation state-specific manner. A common feature of methyllysine recognitions involves a cage of aromatic residues, whereas the ways for discriminating the surrounding amino acid sequence of histones appear to be divergent among different methyllysine "readers." In this study, we focus on the recognition of trimethylated lysine-4 of histone H3 (H3K4me3) by the tandem tudor-like domains of Spindlin1.Mammalian Spindlin1 is a nucleolar protein that localizes to the active ribosomal DNA (rDNA) repeats locus, where it is normally enriched with histone H3K4 and H3K36 methylations, and facilitates rRNA expression (6, 7). Spindlin1 contains three tandem tudor-like domains (8), and we previously demonstrated that the tudor-like domains bind to H3K4me3 in vitro (7). Furthermore, Spindlin1 mutants with impaired H3K4me3 binding showed reduced stimulation of rRNA expression (7). Hence, these observations directly link the ability of H3K4me3 binding with the transcription function of Spindlin1. However, several important aspects of the molecular mechanism of H3K4me3 recognition by Spindlin1 remain outstanding; foremost ones include how Spindlin1 achieves its H3K4me3 specificity and what features distinguish the H3K4me3-binding tudor-like domain from others in Spindlin1. Previous structural studies of tudor domains have yielded some understandings of how they recognize methylated histone ...

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“…1. Tudor-domain-containing proteins or TDRDs have been increasingly studied in relationship with Piwi proteins (Chen et al 2009). These proteins belong to the Tudor protein family and have also been found to play a key role in piRNA biogenesis.…”

Section: Genes Involved In Pirna Generationmentioning

confidence: 99%

MOV10L1 in piRNA processing and gene silencing of retrotransposons during spermatogenesis

Zhu

Zhi

2015

Reproduction

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Piwi-interacting RNAs (piRNAs) are a broad group of non-coding small RNAs with important biological functions in germline cells. It is well known that piRNAs can maintain genome integrity via silencing retrotransposons. Previous studies on the animal models harboring gene deletions have shown that the genes involved in piRNA biogenesis and their defective expression can result in the spermatogenic dysfunction. In the past decade, significant progress has been achieved for piRNAs and their roles in male germ cells. This review addresses the advances on piRNAs and piRNA biogenesis-associated genes, with a particular focus on the Moloney leukemia virus 10-like 1 (MOV10L1) gene, whose role in primary piRNA processing and in the 'ping-pong' cycle during secondary piRNA processing has been illustrated. The biological characteristics of piRNA has been summarized, and emphasis was laid on the roles of MOV10L1 in the mediation of piRNA biogenesis and retrotransposons silencing by DNA methylation. Furthermore, the association between MOV10L1 gene polymorphisms and complete maturation arrest in men has been discussed. Hence, thorough literature review was conducted in order to obtain a greater understanding of the function of MOV10L1 and its mechanisms underlying spermatogenesis in mice and humans. Free Chinese abstract: A Chinese translation of this abstract is freely available at

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Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi

Cited by 166 publications

References 35 publications

Mouse MOV10L1 associates with Piwi proteins and is an essential component of the Piwi-interacting RNA (piRNA) pathway

Mouse MOV10L1 associates with Piwi proteins and is an essential component of the Piwi-interacting RNA (piRNA) pathway

Distinct mode of methylated lysine-4 of histone H3 recognition by tandem tudor-like domains of Spindlin1

MOV10L1 in piRNA processing and gene silencing of retrotransposons during spermatogenesis

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