Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)

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R-HSA-9845323
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Homo sapiens
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Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
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PIWI-interacting RNAs (piRNAs) are short RNAs of 24-31 nucleotides that are produced by cleavage of longer RNAs and amplification by a "ping-pong" mechanism involving rounds of strand hybridization and cleavage (reviewed in Sun et al. 2022). The piRNAs are loaded onto PIWI proteins (PIWIL1, PIWIL2, PIWIL4) that are then guided by base-pairing of the piRNAs to nascent and mature transcripts, where the PIWI:piRNA complexes initiate transcriptional and post-transcriptional silencing, respectively (reviewed in Czech et al. 2018, Onishi et al. 2021, Wang et al. 2023).
In mice, sources of piRNAs include transposon RNAs, long non-coding RNAs, exon transcripts, and RNAs from unannotated regions of the genome (Aravin et al. 2007, 2008). Two populations of piRNAs are observed during mouse development: pre-pachytene piRNAs and pachytene piRNAs (Aravin et al. 2008, Gan et al. 2011). Pre-pachytene piRNAs are present prenatally in prospermatogonial cells and postnatally in spermatogonial cells. Pachytene piRNAs are present in more mature postnatal spermatocytes and spermatids. The piRNAs derived from retroelements comprise about half (Aravin et al. 2008) or less (Gan et al. 2011) of the total pre-pachytene piRNAs and the portion falls sharply from pre-pachytene to pachytene (Gan et al. 2011).
In mice, PIWIL2 (MILI, Piwil2 gene) is first detected in primordial germ cells that have reached the genital ridge and expression persists through meiosis in adults. PIWIL4 (MIWI2, PIWIl4 gene) is present in mouse germ cells during de novo DNA methylation shortly before and after birth. PIWIL1 (MIWI, PIWIL1 gene) is present during later stages of meiosis after birth (Aravin et al. 2008). PIWIL4 and PIWIL2 participate in re-methylation of the genome in mouse germ cells and consequent repression of transposable elements (Carmell et al. 2007, Aravin et al. 2008, Kuramochi-Miyagawa et al. 2008, Zoch et al. 2020). In mice, the piRNAs bound by PIWIL4 bind nascent transcripts of transposable elements and connects to the de novo DNA methylation machinery via SPOCD1 and C19ORF84 to direct DNA methylation to the transposable elements (Zoch et al. 2020, 2024). Mutations in SPOCD1 are associated with infertility in men (Zoch et al. 2024)
Literature References
PubMed ID Title Journal Year
34347367 piRNA- and siRNA-mediated transcriptional repression in Drosophila, mice, and yeast: new insights and biodiversity

Onishi, R, Yamanaka, S, Siomi, MC

EMBO Rep 2021
18381894 DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes

Matsuda, Y, Totoki, Y, Kimura, T, Yamaguchi, Y, Kuramochi-Miyagawa, S, Watanabe, T, Sakaki, Y, Kojima, K, Toyoda, A, Li, E, Sasaki, H, Ijiri, TW, Asada, N, Nakano, T, Okabe, M, Hata, K, Ikawa, M, Gotoh, K

Genes Dev. 2008
17446352 Developmentally regulated piRNA clusters implicate MILI in transposon control

Hannon, GJ, Fejes-Toth, K, Aravin, AA, Sachidanandam, R, Girard, A

Science 2007
38359823 C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line

Kabayama, Y, Heep, M, Conrad, DF, Kliesch, S, Schöpp, T, Stallmeyer, B, Schito, M, O'Bryan, MK, Konieczny, G, Allshire, RC, O'Carroll, D, Tüttelmann, F, Rotte, N, Auchynnikava, T, Rappsilber, J, Cook, AG, Houston, B, Nagirnaja, L, Aston, KI, Zoch, A, Berrens, RV

Mol Cell 2024
36104626 Emerging roles and functional mechanisms of PIWI-interacting RNAs

Wang, X, Simonelig, M, Ramat, A, Liu, MF

Nat Rev Mol Cell Biol 2023
21602304 piRNA profiling during specific stages of mouse spermatogenesis

Wang, L, Liao, S, Zhang, Z, Gan, H, Zhang, W, Lin, X, Han, C

RNA 2011
17395546 MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline

Bourc'his, D, Carmell, MA, Hannon, GJ, van de Kant, HJ, Bestor, TH, de Rooij, DG, Girard, A

Dev. Cell 2007
30476449 piRNA-Guided Genome Defense: From Biogenesis to Silencing

Fabry, MH, Hannon, GJ, Eastwood, EL, Czech, B, Munafò, M, Ciabrelli, F, Kneuss, E

Annu Rev Genet 2018
18922463 A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice

Bourc'his, D, Toth, KF, Hannon, GJ, Bestor, T, Pezic, D, Aravin, AA, Sachidanandam, R, Schaefer, C

Mol. Cell 2008
32674113 SPOCD1 is an essential executor of piRNA-directed de novo DNA methylation

Kabayama, Y, Heep, M, Schöpp, T, Allshire, RC, Vasiliauskaite, L, O'Carroll, D, Pérez-Rico, YA, Auchynnikava, T, Shkumatava, A, Rappsilber, J, Cook, AG, Zoch, A, Berrens, RV

Nature 2020
34724117 The birth of piRNAs: how mammalian piRNAs are produced, originated, and evolved

Li, XZ, Lee, B, Sun, YH

Mamm Genome 2022
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transposable element silencing by piRNA-mediated heterochromatin formation (0141006)
Authored
May, B  (2023-09-24)
Reviewed
Bourc'his, D  (2024-05-14)
Fernandes, LP  (2024-05-14)
Created
May, B  (2023-10-02)
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