9ij4

Structural highlights

Function

PIWL2_MOUSE Endoribonuclease that plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). Plays an essential role in meiotic differentiation of spermatocytes, germ cell differentiation and in self-renewal of spermatogonial stem cells (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). Its presence in oocytes suggests that it may participate in similar functions during oogenesis in females (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). During piRNA biosynthesis, plays a key role in the piRNA amplification loop, also named ping-pong amplification cycle, by acting as a 'slicer-competent' piRNA endoribonuclease that cleaves primary piRNAs, which are then loaded onto 'slicer-incompetent' PIWIL4 (PubMed:22020280, PubMed:23706823, PubMed:26669262). PIWIL2 slicing produces a pre-miRNA intermediate, which is then processed in mature piRNAs, and as well as a 16 nucleotide by-product that is degraded (PubMed:28633017). Required for PIWIL4/MIWI2 nuclear localization and association with secondary piRNAs antisense (PubMed:18381894, PubMed:18922463, PubMed:26669262). Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation (PubMed:19114715). Indirectly modulates expression of genes such as PDGFRB, SLC2A1, ITGA6, GJA7, THY1, CD9 and STRA8 (PubMed:16261612).^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]}

References

1. ↑ Kuramochi-Miyagawa S, Kimura T, Yomogida K, Kuroiwa A, Tadokoro Y, Fujita Y, Sato M, Matsuda Y, Nakano T. Two mouse piwi-related genes: miwi and mili. Mech Dev. 2001 Oct;108(1-2):121-33. PMID:11578866
2. ↑ Kuramochi-Miyagawa S, Kimura T, Ijiri TW, Isobe T, Asada N, Fujita Y, Ikawa M, Iwai N, Okabe M, Deng W, Lin H, Matsuda Y, Nakano T. Mili, a mammalian member of piwi family gene, is essential for spermatogenesis. Development. 2004 Feb;131(4):839-49. doi: 10.1242/dev.00973. Epub 2004 Jan 21. PMID:14736746 doi:http://dx.doi.org/10.1242/dev.00973
3. ↑ Lee JH, Engel W, Nayernia K. Stem cell protein Piwil2 modulates expression of murine spermatogonial stem cell expressed genes. Mol Reprod Dev. 2006 Feb;73(2):173-9. doi: 10.1002/mrd.20391. PMID:16261612 doi:http://dx.doi.org/10.1002/mrd.20391
4. ↑ Aravin AA, Sachidanandam R, Girard A, Fejes-Toth K, Hannon GJ. Developmentally regulated piRNA clusters implicate MILI in transposon control. Science. 2007 May 4;316(5825):744-7. doi: 10.1126/science.1142612. Epub 2007 Apr , 19. PMID:17446352 doi:http://dx.doi.org/10.1126/science.1142612
5. ↑ Kuramochi-Miyagawa S, Watanabe T, Gotoh K, Totoki Y, Toyoda A, Ikawa M, Asada N, Kojima K, Yamaguchi Y, Ijiri TW, Hata K, Li E, Matsuda Y, Kimura T, Okabe M, Sakaki Y, Sasaki H, Nakano T. DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev. 2008 Apr 1;22(7):908-17. doi: 10.1101/gad.1640708. PMID:18381894 doi:http://dx.doi.org/10.1101/gad.1640708
6. ↑ Aravin AA, Sachidanandam R, Bourc'his D, Schaefer C, Pezic D, Toth KF, Bestor T, Hannon GJ. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell. 2008 Sep 26;31(6):785-99. doi: 10.1016/j.molcel.2008.09.003. PMID:18922463 doi:http://dx.doi.org/10.1016/j.molcel.2008.09.003
7. ↑ Unhavaithaya Y, Hao Y, Beyret E, Yin H, Kuramochi-Miyagawa S, Nakano T, Lin H. MILI, a PIWI-interacting RNA-binding protein, is required for germ line stem cell self-renewal and appears to positively regulate translation. J Biol Chem. 2009 Mar 6;284(10):6507-19. Epub 2008 Dec 29. PMID:19114715 doi:http://dx.doi.org/M809104200
8. ↑ De Fazio S, Bartonicek N, Di Giacomo M, Abreu-Goodger C, Sankar A, Funaya C, Antony C, Moreira PN, Enright AJ, O'Carroll D. The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements. Nature. 2011 Oct 23;480(7376):259-63. doi: 10.1038/nature10547. PMID:22020280 doi:http://dx.doi.org/10.1038/nature10547
9. ↑ Di Giacomo M, Comazzetto S, Saini H, De Fazio S, Carrieri C, Morgan M, Vasiliauskaite L, Benes V, Enright AJ, O'Carroll D. Multiple epigenetic mechanisms and the piRNA pathway enforce LINE1 silencing during adult spermatogenesis. Mol Cell. 2013 May 23;50(4):601-8. doi: 10.1016/j.molcel.2013.04.026. PMID:23706823 doi:http://dx.doi.org/10.1016/j.molcel.2013.04.026
10. ↑ Yang Z, Chen KM, Pandey RR, Homolka D, Reuter M, Janeiro BK, Sachidanandam R, Fauvarque MO, McCarthy AA, Pillai RS. PIWI Slicing and EXD1 Drive Biogenesis of Nuclear piRNAs from Cytosolic Targets of the Mouse piRNA Pathway. Mol Cell. 2016 Jan 7;61(1):138-52. doi: 10.1016/j.molcel.2015.11.009. Epub 2015, Dec 6. PMID:26669262 doi:http://dx.doi.org/10.1016/j.molcel.2015.11.009
11. ↑ Wenda JM, Homolka D, Yang Z, Spinelli P, Sachidanandam R, Pandey RR, Pillai RS. Distinct Roles of RNA Helicases MVH and TDRD9 in PIWI Slicing-Triggered Mammalian piRNA Biogenesis and Function. Dev Cell. 2017 Jun 19;41(6):623-637.e9. doi: 10.1016/j.devcel.2017.05.021. PMID:28633017 doi:http://dx.doi.org/10.1016/j.devcel.2017.05.021