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Journal articles on the topic 'Piwi proteins'

Author: Grafiati

Published: 4 June 2021

Last updated: 9 February 2022

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1

Wei, Bang-Hong, Jia-Hao Ni, Tong Yang, Shuang-Li Hao, and Wan-Xi Yang. "PIWIs maintain testis apoptosis to remove abnormal germ cells in Eriocheir sinensis." Reproduction 162, no. 3 (September 1, 2021): 193–207. http://dx.doi.org/10.1530/rep-21-0157.

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PIWI proteins play important roles in germline development in the mammals. However, the functions of PIWIs in crustaceans remain unknown. In the present study, we identified three Piwis from the testis of Eriocheir sinensis (E. sinensis). Three Piwi genes encoded proteins with typical features of PIWI subfamilies and were highly expressed in the testis. Three PIWIs could be detected in the cytoplasm of spermatocytes and spermatids, while in spermatozoa, we could only detect PIWI1 and PIWI3 in the nucleus. The knockdown of PIWIs by dsRNA significantly affected the formation of the nuclei in spermatozoa, which resulted in deviant and irregular nuclei. PIWI defects significantly inhibited the apoptosis of abnormal germ cells through the caspase-dependent apoptosis pathway and p53 pathway. Knockdown of PIWIs inhibited the expression of caspase (Casp) 3, 7, 8, and p53 without affecting Bcl2 (B-cell lymphoma gene 2), Bax (B-cell lymphoma-2-associated X), and BaxI (B-cell lymphoma-2-associated X inhibitor), which further significantly increased abnormal spermatozoa in the knockdown-group crabs. These results show a new role of PIWI proteins in crustaceans that is different from that in mammals. In summary, PIWIs play roles in the formation of the germline nucleus and can maintain apoptosis in abnormal germ cells to remove abnormal germ cells in E. sinensis.

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2

Wang, Chen, Zhen-Zhen Yang, Fang-Hao Guo, Shuo Shi, Xiao-Shuai Han, An Zeng, Haifan Lin, and Qing Jing. "Heat shock protein DNAJA1 stabilizes PIWI proteins to support regeneration and homeostasis of planarian Schmidtea mediterranea." Journal of Biological Chemistry 294, no. 25 (May 10, 2019): 9873–87. http://dx.doi.org/10.1074/jbc.ra118.004445.

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PIWI proteins are key regulators of germline and somatic stem cells throughout different evolutionary lineages. However, how PIWI proteins themselves are regulated remains largely unknown. To identify candidate proteins that interact with PIWI proteins and regulate their stability, here we established a yeast two-hybrid (Y2H) assay in the planarian species Schmidtea mediterranea. We show that DNAJA1, a heat shock protein 40 family member, interacts with the PIWI protein SMEDWI-2, as validated by the Y2H screen and co-immunoprecipitation assays. We found that DNAJA1 is enriched in planarian adult stem cells, the nervous system, and intestinal tissues. DNAJA1-knockdown abolished planarian regeneration and homeostasis, compromised stem cell maintenance and PIWI-interacting RNA (piRNA) biogenesis, and deregulated SMEDWI-1/2 target genes. Mechanistically, we observed that DNAJA1 is required for the stability of SMEDWI-1 and SMEDWI-2 proteins. Furthermore, we noted that human DNAJA1 binds to Piwi-like RNA-mediated gene silencing 1 (PIWIL1) and is required for PIWIL1 stability in human gastric cancer cells. In summary, our results reveal not only an evolutionarily conserved functional link between PIWI and DNAJA1 that is essential for PIWI protein stability and piRNA biogenesis, but also an important role of DNAJA1 in the control of proteins involved in stem cell regulation.

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3

Pammer, Johannes, Heidi Rossiter, Martin Bilban, Leopold Eckhart, Maria Buchberger, Laura Monschein, and Michael Mildner. "PIWIL-2 and piRNAs are regularly expressed in epithelia of the skin and their expression is related to differentiation." Archives of Dermatological Research 312, no. 10 (March 12, 2020): 705–14. http://dx.doi.org/10.1007/s00403-020-02052-7.

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Abstract PIWI proteins play multiple roles in germline stem cell maintenance and self-renewal. PIWI-interacting RNAs (piRNAs) associate with PIWI proteins, form effector complexes and maintain genome integrity and function in the regulation of gene expression by epigenetic modifications. Both are involved in cancer development. In this study, we investigated the expression of PIWIL-2 and piRNAs in normal human skin and epithelial tumors and its regulation during keratinocyte (KC) differentiation. Immunohistochemistry showed that PIWIL-2 was regularly expressed in the epidermis and adnexal tissue with strongest expression in sebaceous glands. Cell culture studies revealed an association of PIWIL-2 expression with the state of differentiated KC. In contrast, the PIWIL-2 expression pattern did not correlate with stem cell compartments or malignancy. piRNAs were consistently detected in KC in vitro by next-generation sequencing and the expression levels of numerous piRNAs were regulated during KC differentiation. Epidermal piRNAs were predominantly derived from processed snoRNAs (C/D-box snoRNAs), tRNAs and protein coding genes. Our data indicate that components of the PIWIL-2—piRNA pathway are present in epithelial cells of the skin and are regulated in the context of KC differentiation, suggesting a role of somatic gene regulation. However, putative roles in the maintenance of stem cell compartments or the development of malignancy in the skin were not supported by this study.

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4

Ishino, Kyoko, Hidetoshi Hasuwa, Jun Yoshimura, Yuka W. Iwasaki, Hidenori Nishihara, Naomi M. Seki, Takamasa Hirano, et al. "Hamster PIWI proteins bind to piRNAs with stage-specific size variations during oocyte maturation." Nucleic Acids Research 49, no. 5 (February 15, 2021): 2700–2720. http://dx.doi.org/10.1093/nar/gkab059.

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Abstract In animal gonads, transposable elements are actively repressed to preserve genome integrity through the PIWI-interacting RNA (piRNA) pathway. In mice, piRNAs are abundantly expressed in male germ cells, and form effector complexes with three distinct PIWIs. The depletion of individual Piwi genes causes male-specific sterility with no discernible phenotype in female mice. Unlike mice, most other mammals have four PIWI genes, some of which are expressed in the ovary. Here, purification of PIWI complexes from oocytes of the golden hamster revealed that the size of the PIWIL1-associated piRNAs changed during oocyte maturation. In contrast, PIWIL3, an ovary-specific PIWI in most mammals, associates with short piRNAs only in metaphase II oocytes, which coincides with intense phosphorylation of the protein. An improved high-quality genome assembly and annotation revealed that PIWIL1- and PIWIL3-associated piRNAs appear to share the 5′-ends of common piRNA precursors and are mostly derived from unannotated sequences with a diminished contribution from TE-derived sequences, most of which correspond to endogenous retroviruses. Our findings show the complex and dynamic nature of biogenesis of piRNAs in hamster oocytes, and together with the new genome sequence generated, serve as the foundation for developing useful models to study the piRNA pathway in mammalian oocytes.

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5

Ross, Robert J., Molly M. Weiner, and Haifan Lin. "PIWI proteins and PIWI-interacting RNAs in the soma." Nature 505, no. 7483 (January 2014): 353–59. http://dx.doi.org/10.1038/nature12987.

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6

Han, Yi-Neng, Yuan Li, Sheng-Qiang Xia, Yuan-Yuan Zhang, Jun-Hua Zheng, and Wei Li. "PIWI Proteins and PIWI-Interacting RNA: Emerging Roles in Cancer." Cellular Physiology and Biochemistry 44, no. 1 (2017): 1–20. http://dx.doi.org/10.1159/000484541.

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P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a type of noncoding RNAs (ncRNAs) and interact with PIWI proteins. piRNAs were primarily described in the germline, but emerging evidence revealed that piRNAs are expressed in a tissue-specific manner among multiple human somatic tissue types as well and play important roles in transposon silencing, epigenetic regulation, gene and protein regulation, genome rearrangement, spermatogenesis and germ stem-cell maintenance. PIWI proteins were first discovered in Drosophila and they play roles in spermatogenesis, germline stem-cell maintenance, self-renewal, retrotransposons silencing and the male germline mobility control. A growing number of studies have demonstrated that several piRNA and PIWI proteins are aberrantly expressed in various kinds of cancers and may probably serve as a novel biomarker and therapeutic target for cancer treatment. Nevertheless, their specific mechanisms and functions need further investigation. In this review, we discuss about the biogenesis, functions and the emerging role of piRNAs and PIWI proteins in cancer, providing novel insights into the possible applications of piRNAs and PIWI proteins in cancer diagnosis and clinical treatment.

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7

Zhang, Heng, Ke Liu, Natsuko Izumi, Haiming Huang, Deqiang Ding, Zuyao Ni, Sachdev S. Sidhu, Chen Chen, Yukihide Tomari, and Jinrong Min. "Structural basis for arginine methylation-independent recognition of PIWIL1 by TDRD2." Proceedings of the National Academy of Sciences 114, no. 47 (November 8, 2017): 12483–88. http://dx.doi.org/10.1073/pnas.1711486114.

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The P-element–induced wimpy testis (PIWI)-interacting RNA (piRNA) pathway plays a central role in transposon silencing and genome protection in the animal germline. A family of Tudor domain proteins regulates the piRNA pathway through direct Tudor domain–PIWI interactions. Tudor domains are known to fulfill this function by binding to methylated PIWI proteins in an arginine methylation-dependent manner. Here, we report a mechanism of methylation-independent Tudor domain–PIWI interaction. Unlike most other Tudor domains, the extended Tudor domain of mammalian Tudor domain-containing protein 2 (TDRD2) preferentially recognizes an unmethylated arginine-rich sequence from PIWI-like protein 1 (PIWIL1). Structural studies reveal an unexpected Tudor domain-binding mode for the PIWIL1 sequence in which the interface of Tudor and staphylococcal nuclease domains is primarily responsible for PIWIL1 peptide recognition. Mutations disrupting the TDRD2–PIWIL1 interaction compromise piRNA maturation via 3′-end trimming in vitro. Our work presented here reveals the molecular divergence of the interactions between different Tudor domain proteins and PIWI proteins.

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8

Arkov, Alexey L. "RNA Selection by PIWI Proteins." Trends in Biochemical Sciences 43, no. 3 (March 2018): 153–56. http://dx.doi.org/10.1016/j.tibs.2017.12.007.

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9

Shi, Shuo, Zhen-Zhen Yang, Sanhong Liu, Fan Yang, and Haifan Lin. "PIWIL1 promotes gastric cancer via a piRNA-independent mechanism." Proceedings of the National Academy of Sciences 117, no. 36 (August 26, 2020): 22390–401. http://dx.doi.org/10.1073/pnas.2008724117.

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Targeted cancer therapy aims to achieve specific elimination of cancerous but not normal cells. Recently, PIWI proteins, a subfamily of the PAZ-PIWI domain (PPD) protein family, have emerged as promising candidates for targeted cancer therapy. PPD proteins are essential for small noncoding RNA pathways. The Argonaute subfamily partners with microRNA and small interfering RNA, whereas the PIWI subfamily partners with PIWI-interacting RNA (piRNA). Both PIWI proteins and piRNA are mostly expressed in the germline and best known for their function in transposon silencing, with no detectable function in mammalian somatic tissues. However, PIWI proteins become aberrantly expressed in multiple types of somatic cancers, thus gaining interest in targeted therapy. Despite this, little is known about the regulatory mechanism of PIWI proteins in cancer. Here we report that one of the four PIWI proteins in humans, PIWIL1, is highly expressed in gastric cancer tissues and cell lines. Knocking out the PIWIL1 gene (PIWIL1-KO) drastically reduces gastric cancer cell proliferation, migration, metastasis, and tumorigenesis. RNA deep sequencing of gastric cancer cell line SNU-1 reveals that KO significantly changes the transcriptome, causing the up-regulation of most of its associated transcripts. Surprisingly, few bona fide piRNAs exist in gastric cancer cells. Furthermore, abolishing the piRNA-binding activity of PIWIL1 does not affect its oncogenic function. Thus, PIWIL1 function in gastric cancer cells is independent of piRNA. This piRNA-independent regulation involves interaction with the UPF1-mediated nonsense-mediated mRNA decay (NMD) mechanism. Altogether, our findings reveal a piRNA-independent function of PIWIL1 in promoting gastric cancer.

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10

Betting, Valerie, Joep Joosten, Rebecca Halbach, Melissa Thaler, Pascal Miesen, and Ronald P. Van Rij. "A piRNA-lncRNA regulatory network initiates responder and trailer piRNA formation during mosquito embryonic development." RNA 27, no. 10 (July 1, 2021): 1155–72. http://dx.doi.org/10.1261/rna.078876.121.

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PIWI-interacting (pi)RNAs are small silencing RNAs that are crucial for the defense against transposable elements in germline tissues of animals. In Aedes aegypti mosquitoes, the piRNA pathway also contributes to gene regulation in somatic tissues, illustrating additional roles for piRNAs and PIWI proteins besides transposon repression. Here, we identify a highly abundant endogenous piRNA (propiR1) that associates with both Piwi4 and Piwi5. PropiR1-mediated target silencing requires base-pairing in the seed region with supplemental base-pairing at the piRNA 3′ end. Yet, propiR1 represses a limited set of targets, among which is the lncRNA AAEL027353 (lnc027353). Slicing of lnc027353 initiates production of responder and trailer piRNAs from the cleavage fragment. Expression of propiR1 commences early during embryonic development and mediates degradation of maternally provided lnc027353. Both propiR1 and its lncRNA target are conserved in the closely related Aedes albopictus mosquito, underscoring the importance of this regulatory network for mosquito development.

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11

Ku, Hsueh-Yen, and Haifan Lin. "PIWI proteins and their interactors in piRNA biogenesis, germline development and gene expression." National Science Review 1, no. 2 (June 1, 2014): 205–18. http://dx.doi.org/10.1093/nsr/nwu014.

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Abstract PIWI-interacting RNAs (piRNAs) are a complex class of small non-coding RNAs that are mostly 24–32 nucleotides in length and composed of at least hundreds of thousands of species that specifically interact with the PIWI protein subfamily of the ARGONAUTE family. Recent studies revealed that PIWI proteins interact with a number of proteins, especially the TUDOR-domain-containing proteins, to regulate piRNA biogenesis and regulatory function. Current research also provides evidence that PIWI proteins and piRNAs are not only crucial for transposon silencing in the germline, but also mediate novel mechanisms of epigenetic programming, DNA rearrangements, mRNA turnover, and translational control both in the germline and in the soma. These new discoveries begin to reveal an exciting new dimension of gene regulation in the cell.

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12

Li, Chunyan, Qiuyue Liu, Xiangyu Wang, Wenping Hu, Deping Han, Joram Mwashigadi Mwacharo, Caihong Wei, Mingxing Chu, and Ran Di. "Expression and localization of PIWI proteins in testis and ovary of domestic sheep." Czech Journal of Animal Science 65, No. 3 (March 31, 2020): 86–96. http://dx.doi.org/10.17221/7/2020-cjas.

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The piRNA-PIWI protein complex plays crucial roles in safeguarding the genome against inordinate transposon mobilization and regulation of embryonic development. A previous study indicated the presence of piRNA in sheep reproductive organs. However, the tissue distribution and cellular localization of PIWI proteins in sheep remains unclear. Therefore the present study aimed to explore the expression profiles of mRNAs of mammalian PIWI proteins (PIWIL1, PIWIL2, PIWIL4 and AGO3) in 9 tissues derived from adult male and female sheep. Results showed the expression of PIWIL1, PIWIL2, and PIWIL4 was significantly higher in the testis and ovary than in the other tissues. Immunohistochemistry analysis of testes indicated that each of the 4 proteins had specific cellular localizations, and some of the localizations were different from those of other species. All the proteins were mainly localized in the primary spermatocytes, suggesting that they are crucial for silencing of transposon to guarantee the integrity of the gamete genome during early stage of spermatogenesis. In the ovaries, the PIWI proteins were mainly localized in oocytes from antral follicles and leukocytes in ovarian blood. Our results provide insights to better understand the functions of PIWI proteins during spermatogenesis, oogenesis and immune defence in sheep.

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13

van Wolfswinkel, J. C. "Piwi and Potency: PIWI Proteins in Animal Stem Cells and Regeneration." Integrative and Comparative Biology 54, no. 4 (June 19, 2014): 700–713. http://dx.doi.org/10.1093/icb/icu084.

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14

Bak, Chong Won, Tae-Ki Yoon, and Youngsok Choi. "Functions of PIWI proteins in spermatogenesis." Clinical and Experimental Reproductive Medicine 38, no. 2 (2011): 61. http://dx.doi.org/10.5653/cerm.2011.38.2.61.

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15

Juliano, C. E., A. Reich, N. Liu, J. Gotzfried, M. Zhong, S. Uman, R. A. Reenan, G. M. Wessel, R. E. Steele, and H. Lin. "PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells." Proceedings of the National Academy of Sciences 111, no. 1 (December 23, 2013): 337–42. http://dx.doi.org/10.1073/pnas.1320965111.

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16

Sellitto, Assunta, Konstantinos Geles, Ylenia D’Agostino, Marisa Conte, Elena Alexandrova, Domenico Rocco, Giovanni Nassa, et al. "Molecular and Functional Characterization of the Somatic PIWIL1/piRNA Pathway in Colorectal Cancer Cells." Cells 8, no. 11 (November 5, 2019): 1390. http://dx.doi.org/10.3390/cells8111390.

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PIWI-like (PIWIL) proteins and small non-coding piRNAs, involved in genome regulation in germline cells, are found aberrantly expressed in human tumors. Gene expression data from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) project, and the European Genome-Phenome Archive (EGA) indicate that the PIWIL1 gene is ectopically activated in a significant fraction of colorectal cancers (CRCs), where this is accompanied by promoter demethylation, together with germline factors required for piRNA production. Starting from this observation, the PIWIL/piRNA pathway was studied in detail in COLO 205 CRC cells, which express significant levels of this protein, to investigate role and significance of ectopic PIWIL1 expression in human tumors. RNA sequencing and cell and computational biology led to the demonstration that PIWIL1 localizes in a nuage-like structure located in the perinuclear region of the cell and that a significant fraction of the piRNAs expressed in these cells are methylated, and, therefore, present in an active form. This was further supported by RNA immunoprecipitation, which revealed how several piRNAs can be found loaded into PIWIL1 to form complexes also comprising their target mRNAs. The mature transcripts associated with the PIWIL–piRNA complex encode key regulatory proteins involved in the molecular mechanisms sustaining colorectal carcinogenesis, suggesting that the PIWI/piRNA pathway may actively contribute to the establishment and/or maintenance of clinico-pathological features of CRCs.

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17

Jeong, Hyeseon, Kyung Hwan Park, Yuri Lee, Ayoung Jeong, Sooji Choi, and Kyung Won Kim. "The Regulation and Role of piRNAs and PIWI Proteins in Cancer." Processes 9, no. 7 (July 14, 2021): 1208. http://dx.doi.org/10.3390/pr9071208.

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P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are regulatory small non-coding RNAs that participate in transposon inactivation, chromatin regulation, and endogenous gene regulation. Numerous genetic and epigenetic factors regulate cell proliferation and tumor metastasis. PIWI proteins and piRNAs have been revealed to function in regulating upstream or downstream of oncogenes or tumor-suppressor genes in cancer tissues. In the present review, we summarize major recent findings in uncovering the regulation and role of PIWI proteins and piRNAs in tumorigenesis and highlight some of the promising applications of specific piRNAs in cancer therapeutics and as cancer biomarkers.

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18

Kim, Iana V., Sebastian Riedelbauch, and Claus-D. Kuhn. "The piRNA pathway in planarian flatworms: new model, new insights." Biological Chemistry 401, no. 10 (September 25, 2020): 1123–41. http://dx.doi.org/10.1515/hsz-2019-0445.

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AbstractPIWI-interacting RNAs (piRNAs) are small regulatory RNAs that associate with members of the PIWI clade of the Argonaute superfamily of proteins. piRNAs are predominantly found in animal gonads. There they silence transposable elements (TEs), regulate gene expression and participate in DNA methylation, thus orchestrating proper germline development. Furthermore, PIWI proteins are also indispensable for the maintenance and differentiation capabilities of pluripotent stem cells in free-living invertebrate species with regenerative potential. Thus, PIWI proteins and piRNAs seem to constitute an essential molecular feature of somatic pluripotent stem cells and the germline. In keeping with this hypothesis, both PIWI proteins and piRNAs are enriched in neoblasts, the adult stem cells of planarian flatworms, and their presence is a prerequisite for the proper regeneration and perpetual tissue homeostasis of these animals. The piRNA pathway is required to maintain the unique biology of planarians because, in analogy to the animal germline, planarian piRNAs silence TEs and ensure stable genome inheritance. Moreover, planarian piRNAs also contribute to the degradation of numerous protein-coding transcripts, a function that may be critical for neoblast differentiation. This review gives an overview of the planarian piRNA pathway and of its crucial function in neoblast biology.

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19

Erber, Ramona, Julia Meyer, Helge Taubert, Peter A. Fasching, Sven Wach, Lothar Häberle, Paul Gaß, et al. "PIWI-Like 1 and PIWI-Like 2 Expression in Breast Cancer." Cancers 12, no. 10 (September 24, 2020): 2742. http://dx.doi.org/10.3390/cancers12102742.

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PIWI-like 1 and PIWI-like 2 play a role in stem cell self-renewal, and enhanced expression has been reported for several tumor entities. However, few studies have investigated PIWI-like 1 and PIWI-like 2 expressions in breast cancer subtypes regarding prognosis. Therefore, we examined protein expression in a large consecutive cohort of breast cancer patients and correlated it to breast cancer subtypes and survival outcome. PIWI-like 1 and PIWI-like 2 expressions were evaluated using immunohistochemistry in a cohort of 894 breast cancer patients, of whom 363 were eligible for further analysis. Percentage and intensity of stained tumor cells were analyzed and an immunoreactive score (IRS) was calculated. The interaction of PIWI-like 1 and PIWI-like 2 showed a prognostic effect on survival. For the combination of high PIWI-like 1 and low PIWI-like 2 expressions, adjusted hazard ratios (HRs) were significantly higher with regard to overall survival (OS) (HR 2.92; 95% confidence interval (CI) 1.24, 6.90), disease-free survival (DFS) (HR 3.27; 95% CI 1.48, 7.20), and distant disease-free survival (DDFS) (HR 7.64; 95% CI 2.35, 24.82). Both proteins were significantly associated with molecular-like and PAM50 subgroups. Combining high PIWI-like 1 and low PIWI-like 2 expressions predicted poorer prognosis and both markers were associated with aggressive molecular subtypes.

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Tan, Y., L. Liu, M. Liao, C. Zhang, S. Hu, M. Zou, M. Gu, and X. Li. "Emerging roles for PIWI proteins in cancer." Acta Biochimica et Biophysica Sinica 47, no. 5 (April 7, 2015): 315–24. http://dx.doi.org/10.1093/abbs/gmv018.

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21

Seto, Anita G., Robert E. Kingston, and Nelson C. Lau. "The Coming of Age for Piwi Proteins." Molecular Cell 26, no. 5 (June 2007): 603–9. http://dx.doi.org/10.1016/j.molcel.2007.05.021.

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22

Meseure, Didier, Sophie Vacher, Sabah Boudjemaa, Marick Laé, André Nicolas, Renaud Leclere, Walid Chemlali, et al. "Biopathological Significance of PIWI–piRNA Pathway Deregulation in Invasive Breast Carcinomas." Cancers 12, no. 10 (September 30, 2020): 2833. http://dx.doi.org/10.3390/cancers12102833.

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The PIWI proteins emerging in the development of human cancers, edify PIWI-piRNA ribonucleoproteic complexes acting as pivotal regulators of genome integrity, differentiation and homeostasis. The aim of this study is to analyze the four PIWILs gene expression in invasive breast carcinomas (IBCs): at RNA level using quantitative RT-PCR (n = 526) and protein level using immunohistochemistry (n = 150). In normal breast tissue, PIWILs 2 and 4 were solely expressed, whereas an abnormal emergence of PIWIL1 and 3 was observed in respectively 30% and 6% of IBCs. Conversely, PIWIL2 was underexpressed in 48.3% and PIWIL4 downregulated in 43.3% of IBCs. Significant positive associations were observed between PIWIL4 underexpression, HR+ status and HR+ ERBB2+ molecular subtype and PIWIL2 underexpression, PR- status, ERBB2- status and molecular subtype. Similar patterns of PIWIL deregulation were observed in a multitumoral panel, suggesting a generic mechanism in most cancers. PIWIL2-4 underexpression was mainly regulated at epigenetic or post-transcriptional levels. PIWIL2 underexpression was significantly associated with DNA methylation and strong cytotoxic immune response. PIWIL2-4 were mainly associated with genes implicated in cell proliferation. As a result of this study, characterization of the PIWIL-piRNA pathway in IBCs opens interesting therapeutic perspectives using piRNAs, hypomethylating drugs, checkpoints immunotherapies and anti-PIWIL 1–3 antibodies.

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23

Franco Neto, Walter Félix, Murilo Tavares Amorim, Karla Fabiane Lopes de Melo, Gustavo Moraes Holanda, Jardel Fábio Lopes Ferreira, and Samir Mansour Moraes Casseb. "Expression profile of the PIWI mRNAs protein family in human cells experimentally infected with Dengue Virus 4." Research, Society and Development 10, no. 3 (March 17, 2021): e32010313371. http://dx.doi.org/10.33448/rsd-v10i3.13371.

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Objective: Evaluate the messenger RNAs (mRNA) PIWI proteins expression during infection with VDEN 4 in human hepatocyte cells. Materials and Methods: VDEN4 strain H778494 (JQ513335) was used, which was stored in Aedes albopictus cell culture (Clone C6 / 36) at the Arbovirology and Hemorrhagic Fevers section of the Evandro Chagas Institute. The techniques of cell cultures, stock (C6/36), inoculation, extraction, viral load quantification, RTqPCR and statistical analyzes were performed at the Viral Biogenesis Laboratory. Results: According to the results obtained, two cells (HepG2 and Huh7.5) demonstrated a higher level of viral replication at 72 hours post infection (hpi). The PIWI 2 target alter its mRNA expression during VDEN4 infection. The PIWI 4 target expression, was observed an altered expression in the infected cells. Thus, it was found that they are in different poles, while the viral load in the first three days showed high expression. The expression of mRNA was low in relation to the normal rate given by the uninfected cells. Conclusion: In our findings, it was observed that PIWI2 and 4 proteins have an inverse relationship to the viral infection process by VDEN4, when there is an increase in viral replication, these two proteins end up having a significant reduction in their expression. Probably, this reduction of expression is involved with the biogenesis process of apoptosis-regulating microRNAs.

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Pleštilová, Lenka, Michel Neidhart, Giancarlo Russo, Mojca Frank-Bertoncelj, Caroline Ospelt, Adrian Ciurea, Christoph Kolling, et al. "Expression and Regulation of PIWIL-Proteins and PIWI-Interacting RNAs in Rheumatoid Arthritis." PLOS ONE 11, no. 11 (November 28, 2016): e0166920. http://dx.doi.org/10.1371/journal.pone.0166920.

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25

Zhang, Yuhan, Weiwei Liu, Ronghong Li, Jiaqi Gu, Ping Wu, Chao Peng, Jinbiao Ma, Ligang Wu, Yang Yu, and Ying Huang. "Structural insights into the sequence-specific recognition of Piwi by Drosophila Papi." Proceedings of the National Academy of Sciences 115, no. 13 (March 12, 2018): 3374–79. http://dx.doi.org/10.1073/pnas.1717116115.

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The Tudor domain-containing (Tdrd) family proteins play a critical role in transposon silencing in animal gonads by recognizing the symmetrically dimethylated arginine (sDMA) on the (G/A)R motif of the N-terminal of PIWI family proteins via the eTud domains. Papi, also known as “Tdrd2,” is involved in Zucchini-mediated PIWI-interacting RNA (piRNA) 3′-end maturation. Intriguingly, a recent study showed that, in papi mutant flies, only Piwi-bound piRNAs increased in length, and not Ago3-bound or Aub-bound piRNAs. However, the molecular and structural basis of the Papi–Piwi complex is still not fully understood, which limits mechanistic understanding of the function of Papi in piRNA biogenesis. In the present study, we determined the crystal structures of Papi-eTud in the apo form and in complex with a peptide containing unmethylated or dimethylated R10 residues. Structural and biochemical analysis showed that the Papi interaction region on the Drosophila Piwi contains an RGRRR motif (R7–R11) distinct from the consensus (G/A)R motif recognized by canonical eTud. Mass spectrometry results indicated that Piwi is the major binding partner of Papi in vivo. The papi mutant flies suffered from both fertility and transposon-silencing defects, supporting the important role conferred to Papi in piRNA 3′ processing through direct interaction with Piwi proteins.

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Cora, E., R. R. Pandey, J. Xiol, J. Taylor, R. Sachidanandam, A. A. McCarthy, and R. S. Pillai. "The MID-PIWI module of Piwi proteins specifies nucleotide- and strand-biases of piRNAs." RNA 20, no. 6 (April 22, 2014): 773–81. http://dx.doi.org/10.1261/rna.044701.114.

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Andress, Arlise, Yanxia Bei, Bryan R. Fonslow, Ritika Giri, Yilong Wu, John R. Yates, and Richard W. Carthew. "Spindle-E cycling between nuage and cytoplasm is controlled by Qin and PIWI proteins." Journal of Cell Biology 213, no. 2 (April 18, 2016): 201–11. http://dx.doi.org/10.1083/jcb.201411076.

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Transposable elements (TEs) are silenced in germ cells by a mechanism in which PIWI proteins generate and use PIWI-interacting ribonucleic acid (piRNA) to repress expression of TE genes. piRNA biogenesis occurs by an amplification cycle in microscopic organelles called nuage granules, which are localized to the outer face of the nuclear envelope. One cofactor required for amplification is the helicase Spindle-E (Spn-E). We found that the Spn-E protein physically associates with the Tudor domain protein Qin and the PIWI proteins Aubergine (Aub) and Argonaute3 (Ago3). Spn-E and Qin proteins are mutually dependent for their exit from nuage granules, whereas Spn-E and both Aub and Ago3 are mutually dependent for their entry or retention in nuage. The result is a dynamic cycling of Spn-E and its associated factors in and out of nuage granules. This implies that nuage granules can be considered to be hubs for active, mobile, and transient complexes. We suggest that this is in some way coupled with the execution of the piRNA amplification cycle.

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Liu, Xiuqin, Jun Ding, and Fuzhou Gong. "piRNA identification based on motif discovery." Mol. BioSyst. 10, no. 12 (2014): 3075–80. http://dx.doi.org/10.1039/c4mb00447g.

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Piwi-interacting RNA (piRNA) is a class of small non-coding RNAs about 24 to 32 nucleotides long, associated with PIWI proteins, which are involved in germline development, transposon silencing, and epigenetic regulation.

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Mani, Sneha Ramesh, Heather Megosh, and Haifan Lin. "PIWI proteins are essential for early Drosophila embryogenesis." Developmental Biology 385, no. 2 (January 2014): 340–49. http://dx.doi.org/10.1016/j.ydbio.2013.10.017.

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Litwin, Monika, Anna Szczepańska-Buda, Aleksandra Piotrowska, Piotr Dzięgiel, and Wojciech Witkiewicz. "The meaning of PIWI proteins in cancer development." Oncology Letters 13, no. 5 (March 28, 2017): 3354–62. http://dx.doi.org/10.3892/ol.2017.5932.

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Li, W., J. Martinez Useros, M. J. Fernández-Aceñero, N. García Carbonero, and J. García-Foncillas. "PIWI proteins play oncogenic functions in pancreatic cancer." Annals of Oncology 30 (February 2019): i1. http://dx.doi.org/10.1093/annonc/mdz025.

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Kibanov, Mikhail V., Ksenia S. Egorova, Sergei S. Ryazansky, Olesia A. Sokolova, Alexei A. Kotov, Oxana M. Olenkina, Anastasia D. Stolyarenko, Vladimir A. Gvozdev, and Ludmila V. Olenina. "A novel organelle, the piNG-body, in the nuage of Drosophila male germ cells is associated with piRNA-mediated gene silencing." Molecular Biology of the Cell 22, no. 18 (September 15, 2011): 3410–19. http://dx.doi.org/10.1091/mbc.e11-02-0168.

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Proteins of the PIWI subfamily Aub and AGO3 associated with the germline-specific perinuclear granules (nuage) are involved in the silencing of retrotransposons and other selfish repetitive elements in the Drosophila genome. PIWI proteins and their 25- to 30-nt PIWI-interacting RNA (piRNAs) are considered as key participants of the piRNA pathway. Using immunostaining, we found a large, nuage-associated organelle in the testes, the piNG-body (piRNA nuage giant body), which was significantly more massive than an ordinary nuage granule. This body contains known ovarian nuage proteins, including Vasa, Aub, AGO3, Tud, Spn-E, Bel, Squ, and Cuff, as well as AGO1, the key component of the microRNA pathway. piNG-bodies emerge at the primary spermatocyte stage of spermatogenesis during the period of active transcription. Aub, Vasa, and Tud are located at the periphery of the piNG-body, whereas AGO3 is found in its core. Mutational analysis revealed that Vasa, Aub, and AGO3 were crucial for both the maintenance of the piNG-body structure and the silencing of selfish Stellate repeats. The piNG-body destruction caused by csul mutations that abolish specific posttranslational symmetrical arginine methylation of PIWI proteins is accompanied by strong derepression of Stellate genes known to be silenced via the piRNA pathway.

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Zeng, Qian, Jiaodi Cai, Hengquan Wan, Simin Zhao, Yao Tan, Chi Zhang, and Shunlin Qu. "PIWI-interacting RNAs and PIWI proteins in diabetes and cardiovascular disease: Molecular pathogenesis and role as biomarkers." Clinica Chimica Acta 518 (July 2021): 33–37. http://dx.doi.org/10.1016/j.cca.2021.03.011.

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Mirzaei, Khaled, Bahman Bahramnejad, Mohammad Hasan Shamsifard, and Wahid Zamani. "In SilicoIdentification, Phylogenetic and Bioinformatic Analysis of Argonaute Genes in Plants." International Journal of Genomics 2014 (2014): 1–17. http://dx.doi.org/10.1155/2014/967461.

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Argonaute protein family is the key players in pathways of gene silencing and small regulatory RNAs in different organisms. Argonaute proteins can bind small noncoding RNAs and control protein synthesis, affect messenger RNA stability, and even participate in the production of new forms of small RNAs. The aim of this study was to characterize and perform bioinformatic analysis of Argonaute proteins in 32 plant species that their genome was sequenced. A total of 437 Argonaute genes were identified and were analyzed based on lengths, gene structure, and protein structure. Results showed that Argonaute proteins were highly conserved across plant kingdom. Phylogenic analysis divided plant Argonautes into three classes. Argonaute proteins have three conserved domains PAZ, MID and PIWI. In addition to three conserved domains namely, PAZ, MID, and PIWI, we identified few more domains in AGO of some plant species. Expression profile analysis of Argonaute proteins showed that expression of these genes varies in most of tissues, which means that these proteins are involved in regulation of most pathways of the plant system. Numbers of alternative transcripts of Argonaute genes were highly variable among the plants. A thorough analysis of large number of putative Argonaute genes revealed several interesting aspects associated with this protein and brought novel information with promising usefulness for both basic and biotechnological applications.

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Zheng, K., J. Xiol, M. Reuter, S. Eckardt, N. A. Leu, K. J. McLaughlin, A. Stark, R. Sachidanandam, R. S. Pillai, and P. J. Wang. "Mouse MOV10L1 associates with Piwi proteins and is an essential component of the Piwi-interacting RNA (piRNA) pathway." Proceedings of the National Academy of Sciences 107, no. 26 (June 1, 2010): 11841–46. http://dx.doi.org/10.1073/pnas.1003953107.

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Watanabe, Toshiaki, and Haifan Lin. "Posttranscriptional Regulation of Gene Expression by Piwi Proteins and piRNAs." Molecular Cell 56, no. 1 (October 2014): 18–27. http://dx.doi.org/10.1016/j.molcel.2014.09.012.

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Wasik, Kaja A., Oliver H. Tam, Simon R. Knott, Ilaria Falciatori, Molly Hammell, Vasily V. Vagin, and Gregory J. Hannon. "RNF17 blocks promiscuous activity of PIWI proteins in mouse testes." Genes & Development 29, no. 13 (June 26, 2015): 1403–15. http://dx.doi.org/10.1101/gad.265215.115.

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Izumi, N., S. Kawaoka, S. Yasuhara, Y. Suzuki, S. Sugano, S. Katsuma, and Y. Tomari. "Hsp90 facilitates accurate loading of precursor piRNAs into PIWI proteins." RNA 19, no. 7 (May 16, 2013): 896–901. http://dx.doi.org/10.1261/rna.037200.112.

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Roovers, Elke F., David Rosenkranz, Mahdi Mahdipour, Chung-Ting Han, Nannan He, Susana M. Chuva de Sousa Lopes, Lucette A. J. van der Westerlaken, et al. "Piwi Proteins and piRNAs in Mammalian Oocytes and Early Embryos." Cell Reports 10, no. 12 (March 2015): 2069–82. http://dx.doi.org/10.1016/j.celrep.2015.02.062.

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Tushir, Jogender S., Phillip D. Zamore, and Zhao Zhang. "SnapShot: Mouse piRNAs, PIWI Proteins, and the Ping-Pong Cycle." Cell 139, no. 4 (November 2009): 830–830. http://dx.doi.org/10.1016/j.cell.2009.10.042.

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Tushir, Jogender S., Phillip D. Zamore, and Zhao Zhang. "SnapShot: Fly piRNAs, PIWI Proteins, and the Ping-Pong Cycle." Cell 139, no. 3 (October 2009): 634–634. http://dx.doi.org/10.1016/j.cell.2009.10.021.

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Czech, Benjamin, Marzia Munafò, Filippo Ciabrelli, Evelyn L. Eastwood, Martin H. Fabry, Emma Kneuss, and Gregory J. Hannon. "piRNA-Guided Genome Defense: From Biogenesis to Silencing." Annual Review of Genetics 52, no. 1 (November 23, 2018): 131–57. http://dx.doi.org/10.1146/annurev-genet-120417-031441.

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PIWI-interacting RNAs (piRNAs) and their associated PIWI clade Argonaute proteins constitute the core of the piRNA pathway. In gonadal cells, this conserved pathway is crucial for genome defense, and its main function is to silence transposable elements. This is achieved through posttranscriptional and transcriptional gene silencing. Precursors that give rise to piRNAs require specialized transcription and transport machineries because piRNA biogenesis is a cytoplasmic process. The ping-pong cycle, a posttranscriptional silencing mechanism, combines the cleavage-dependent silencing of transposon RNAs with piRNA production. PIWI proteins also function in the nucleus, where they scan for nascent target transcripts with sequence complementarity, instructing transcriptional silencing and deposition of repressive chromatin marks at transposon loci. Although studies have revealed numerous factors that participate in each branch of the piRNA pathway, the precise molecular roles of these factors often remain unclear. In this review, we summarize our current understanding of the mechanisms involved in piRNA biogenesis and function.

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43

Sato, Kaoru, and Mikiko C. Siomi. "Piwi-interacting RNAs: biological functions and biogenesis." Essays in Biochemistry 54 (April 30, 2013): 39–52. http://dx.doi.org/10.1042/bse0540039.

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The integrity of the germline genome must be maintained to achieve successive generations of a species, because germline cells are the only source for transmitting genetic information to the next generation. Accordingly, the germline has acquired a system dedicated to protecting the genome from ‘injuries’ caused by harmful selfish nucleic acid elements, such as TEs (transposable elements). Accumulating evidence shows that a germline-specific subclass of small non-coding RNAs, piRNAs (piwi-interacting RNAs), are necessary for silencing TEs to protect the genome in germline cells. To silence TEs post-transcriptionally and/or transcriptionally, mature piRNAs are loaded on to germline-specific Argonaute proteins, or PIWI proteins, to form the piRISC (piRNA-induced silencing complex). The present chapter will highlight insights into the molecular mechanisms underlying piRISC-mediated silencing and piRNA biogenesis, and discuss a possible link with tumorigenesis, particularly in Drosophila.

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Fukuhara, Satoshi, Hiroshi Nishimasu, Luc Bonnefond, Naoki Matsumoto, Ryuichiro Ishitani, and Osamu Nureki. "Expression, purification, crystallization and preliminary X-ray crystallographic analysis of Zucchini fromDrosophila melanogaster." Acta Crystallographica Section F Structural Biology and Crystallization Communications 68, no. 11 (October 30, 2012): 1346–50. http://dx.doi.org/10.1107/s1744309112038936.

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PIWI-interacting RNAs (piRNAs) bind PIWI proteins and silence transposons to maintain the genomic integrity of germ cells. Zucchini (Zuc), a phospholipase D superfamily member, is conserved among animals and is implicated in piRNA biogenesis. However, the underlying mechanism by which Zuc participates in piRNA biogenesis remains elusive.Drosophila melanogasterZuc (DmZuc) was expressed inEscherichia coli, purified and crystallized. X-ray diffraction data were collected to 1.75 Å resolution. The crystal belonged to space groupP21, with unit-cell parametersa= 55.0,b= 71.2,c= 56.3 Å, β = 107.9°.

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Girard, Angélique, Ravi Sachidanandam, Gregory J. Hannon, and Michelle A. Carmell. "A germline-specific class of small RNAs binds mammalian Piwi proteins." Nature 442, no. 7099 (June 4, 2006): 199–202. http://dx.doi.org/10.1038/nature04917.

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Virgili, G., I. Varlan, K. Illes, and B. Nagar. "Structural studies on piRNA recognition by mammalian PIWI-like Argonaute proteins." Acta Crystallographica Section A Foundations of Crystallography 67, a1 (August 22, 2011): C658. http://dx.doi.org/10.1107/s0108767311083371.

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Yakushev, E. Y., O. A. Sokolova, V. A. Gvozdev, and M. S. Klenov. "Multifunctionality of PIWI proteins in control of germline stem cell fate." Biochemistry (Moscow) 78, no. 6 (June 2013): 585–91. http://dx.doi.org/10.1134/s0006297913060047.

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Balmeh, Negar, Samira Mahmoudi, and Anasik Karabedianhajiabadi. "piRNAs and PIWI proteins: From biogenesis to their role in cancer." Gene Reports 22 (March 2021): 101013. http://dx.doi.org/10.1016/j.genrep.2020.101013.

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Huang, Ying, and Bowen Yu. "Structural studies of Rhino protein in piRNA biogenesis." Acta Crystallographica Section A Foundations and Advances 70, a1 (August 5, 2014): C1589. http://dx.doi.org/10.1107/s2053273314084101.

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Small-RNA-guided gene regulation is a common biological process in eukaryotic cells. Animal germ cells are characterized by an intriguing small-RNA-mediated gene-silencing mechanism known as PIWI pathway. PIWI-interacting RNAs (piRNAs) are small, 21-30 nt single-stranded RNAs that associate with PIWI proteins. The function of piRNA is silencing transposon elements in germ line cells to keep the genome integrity since germ line cells are the only source for transmitting genetic information to the next generation. For a long time the biogenesis of piRNA and the mechanism of how it functions remains unclear. The biogenesis of piRNAs is quite different from that of other small-RNA pathways, which is independent of Dicer. piRNA biogenesis occurs through both primary and secondary pathway (or called ping-pong cycle). In drosophila transcripts from heterochromatic clusters are processed into primary piRNAs. A particularly fast evolving homologue of heterochromatin protein 1 (HP1) called Rhino binds to dual-strand piRNA clusters and is required for their production. But how does Rhino recognize histone H3 trimethylated on lysine 9? What's the difference between Rhino and other HP1 proteins? Here we show the crystal structure of Rhino both in apo form and complex form with H3K9me3. We observed a unique dimer interface in Rhino and a domain-swapping in conformational change. These findings provide insights into the molecular mechanism of the specificity of Rhino recognizing histone H3K9me3 and its function in piRNA biogenesis.

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Russell, Stewart, Mehool Patel, Graham Gilchrist, Leanne Stalker, Daniel Gillis, David Rosenkranz, and Jonathan LaMarre. "Bovine piRNA-like RNAs are associated with both transposable elements and mRNAs." Reproduction 153, no. 3 (March 2017): 305–18. http://dx.doi.org/10.1530/rep-16-0620.

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PIWI proteins and their associated piRNAs have been the focus of intensive research in the past decade; therefore, their participation in the maintenance of genomic integrity during spermatogenesis has been well established. Recent studies have suggested important roles for the PIWI/piRNA system outside of gametogenesis, based on the presence of piRNAs and PIWI proteins in several somatic tissues, cancers, and the early embryo. Here, we investigated the small RNA complement present in bovine gonads, gametes, and embryos through next-generation sequencing. A distinct piRNA population was present in the testis as expected. However, we also found a large population of slightly shorter, 24–27 nt piRNA-like RNA (pilRNAs) in pools of oocytes and zygotes. These oocyte and embryo pilRNAs exhibited many of the canonical characteristics of piRNAs including a 1U bias, the presence of a ‘ping-pong’ signature, genomic clustering, and transposable element targeting. Some of the major transposons targeted by oocyte and zygote pilRNA were from the LINE RTE and ERV1 classes. We also identified pools of pilRNA potentially derived from, or targeted at, specific mRNA sequences. We compared the frequency of these gene-associated pilRNAs to the fold change in the expression of respective mRNAs from two previously reported transcriptome datasets. We observed significant negative correlations between the number of pilRNAs targeting mRNAs, and their fold change in expression between the 4–8 cell and 8–16 cell stages. Together, these results represent one of the first characterizations of the PIWI/piRNA pathway in the translational bovine model, and in the novel context of embryogenesis.

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