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

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-9845323

PubChem

R-HSA-9845323

Description

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)

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Displaying entries **1 - 10** of 46 in total

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UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O14497	AT-rich interactive domain-containing protein 1A	ARID1A BAF250 BAF250A C1orf4 OSA1 SMARCF1	view
O60814	Histone H2B type 1-K	H2BC12 H2BFT HIRIP1 HIST1H2BK	view
O75177	Calcium-responsive transactivator	CREST KIAA0693 SS18L1	view
O95983	Methyl-CpG-binding domain protein 3	MBD3	view
O96019	Actin-like protein 6A	ACTL6A BAF53 BAF53A INO80K	view
P04908	Histone H2A type 1-B/E	H2AC4; H2AC8 H2AFA H2AFM HIST1H2AB HIST1H2AE	view
P06899	Histone H2B type 1-J	H2BC11 H2BFR HIST1H2BJ	view
P16104	Histone H2AX	H2AFX H2AX	view
P23527	Histone H2B type 1-O	H2BC17 H2BFH H2BFN HIST1H2BO	view
P33778	Histone H2B type 1-B	H2BC3 H2BFF HIST1H2BB	view

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