A Role for Piwi and piRNAs in Germ Cell Maintenance and Transposon Silencing in Zebrafish

Houwing, Saskia; Kamminga, Leonie M.; Berezikov, Eugène; Cronembold, Daniela; Girard, Angélique; Elst, Hans van den; Filippov, Dmitri V.; Blaser, Heiko; Raz, Erez; Moens, Cecilia B.; Plasterk, Ronald H.A.; Hannon, Gregory J.; Draper, Bruce W.; Ketting, René F.

doi:10.1016/j.cell.2007.03.026

Cited by 1,026 publications

(1,048 citation statements)

References 53 publications

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“…Proteins with Piwi domains have been described as components of ribonucleoprotein complexes that act in the microRNA/ RNA interference pathway of gene silencing (Fetzer et al, 2002, Lingel et al, 2005. Recently, it was shown that the Piwi gene family are associated with a new class of small RNAs socalled 'piwi-interacting RNAs' (piRNAs) in mammalian spermatogenesis (Hall et al, 2005, Houwing et al, 2007, Hutvagner et al, 2008, Peters et al, 2007, which is one of gene expressing regulatory small non-coding RNAs (ncRNAs). Small ncRNAs are naturally conserved regulators of gene expression described in almost all eukaryotic species including humans (Elbashir et al, 2001, Meister et al, 2004, Sana et al, 2012.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Hiwi Promotes Growth of Human Breast Cancer Cells

Wang¹,

Wang²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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The Piwi subfamily comprises two argonaute (Ago) family proteins, which are defined by the presence of PAZ and Piwi domains, with well known roles in RNA silencing. Hiwi, a human Piwi subfamily member, has been shown to play essential roles in stem cell self-renewal and gametogenesis. Recently, accumulating reports have indicated that abnormal hiwi expression is associated with poorer prognosis of multiple types of human cancers, including examples in the breast. However, little is known about details of the oncogenic role of hiwi in breast cancers. In present study, we confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines at both mRNA and protein levels. Thus both RT-qPCR and Western blot data revealed significantly higher hiwi in intratumor than peritumor specimens, overexpression being associated with tumor size, lymph node metastasis and histological grade. Hiwi overexpression was also identified in breast cancer cell lines, MDA-MB-231 and MCF-7, and gain-of-function and loss-of-function strategies were adopted to identify the role of hiwi in the MCF-7 cell growth. Results demonstrated that hiwi expression in MCF-7 cells was significantly up-or down-regulated by the two strategies. We next evaluated the influence of hiwi overexpression or knockdown on the growth of breast cancer cells. Both cell count and colony formation assays confirmed promoting roles of hiwi in MCF-7 cells, which could be inhibited by hiwi specific blockage by siRNAs. In summary, the present study confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines, and provided evidence of promotion by hiwi of cell growth. The results imply an oncogenic role of hiwi in breast cancers.

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Section: Discussionmentioning

confidence: 99%

Overexpression of Hiwi Promotes Growth of Human Breast Cancer Cells

Wang¹,

Wang²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…14,15 Notably, various mRNA degradative enzymes are found in mRNP granules besides P-bodies, such as Xrn1 in stress granules 11 and Drosophila/mouse spermatid nuage, 65 Dcp1/ Dcp2 in various germ granules, [66][67][68] and several Argonaute proteins with endonuclease activity in stress granules, 69 and various germ granules. [70][71][72][73] Whether mRNA degradation occurs in mRNP granules besides P-bodies remains poorly studied.…”

Section: Mrnp Granules Assemble Via Common Mechanismsmentioning

confidence: 99%

mRNP granules

2014

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“…We deemed this analysis necessary since this modification is thought to maintain the stability of piRNAs [23][24][25][26][27][28]. In addition, the PIWI proteins in Drosophila interact with the piRNA methyltransferase, which in turn may be necessary for the methylation of piRNAs [27].…”

Section: Mili-associated Pirnas Are Upregulated But Not Downregulatedmentioning

confidence: 99%

piRNA biogenesis during adult spermatogenesis in mice is independent of the ping-pong mechanism

2012

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piRNAs, a class of small non-coding RNAs associated with PIWI proteins, have broad functions in germline development, transposon silencing, and epigenetic regulation. In diverse organisms, a subset of piRNAs derived from repeat sequences are produced via the interplay between two PIWI proteins. This mechanism, termed "ping-pong" cycle, operates among the PIWI proteins of the primordial mouse testis; however, its involvement in postnatal testes remains elusive. Here we show that adult testicular piRNAs are produced independent of the ping-pong mechanism. We identified and characterized large populations of piRNAs in the adult and postnatal developing testes associated with MILI and MIWI, the only PIWI proteins detectable in these testes. No interaction between MILI and MIWI or sequence feature for the ping-pong mechanism among their piRNAs was detected in the adult testis. The majority of MILI-and MIWI-associated piRNAs originate from the same DNA strands within the same loci. Both populations of piRNAs are biased for 5′ Uracil but not for Adenine on the 10th nucleotide position, and display no complementarity. Furthermore, in Miwi mutants, MILI-associated piRNAs are not downregulated, but instead upregulated. These results indicate that the adult testicular piRNAs are predominantly, if not exclusively, produced by a primary processing mechanism instead of the ping-pong mechanism. In this primary pathway, biogenesis of MILI-and MIWIassociated piRNAs may compete for the same precursors; the types of piRNAs produced tend to be non-selectively dictated by the available precursors in the cell; and precursors with introns tend to be spliced before processed into piRNAs.

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A Role for Piwi and piRNAs in Germ Cell Maintenance and Transposon Silencing in Zebrafish

Cited by 1,026 publications

References 53 publications

Overexpression of Hiwi Promotes Growth of Human Breast Cancer Cells

Overexpression of Hiwi Promotes Growth of Human Breast Cancer Cells

mRNP granules

piRNA biogenesis during adult spermatogenesis in mice is independent of the ping-pong mechanism

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