PIWI-interacting RNA (piRNA) biogenesis

Stable Identifier
R-HSA-5601884
Type
Pathway
Species
Homo sapiens
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Summation

In germ cells of humans and mice, precursors of PIWI-interacting RNAs (piRNAs) are transcribed from a few hundred sequence clusters, as well as individual transposons, intergenic regions, and genes in the genome. These longer transcripts are processed to yield piRNAs of 26-30 nucleotides independently of DICER, the enzyme responsible for microRNAs (miRNAs) and small interfering RNAs (siRNAs) (reviewed in Girard and Hannon 2008, Siomi et al. 2011, Ishizu et al. 2012, Pillai and Chuma 2012, Bortvin 2013, Chuma and Nakano 2013, Sato and Siomi 2013). The initial step in processing long transcripts to piRNAs is cleavage by PLD6 (MitoPLD), which generates the mature 5' end. The cleavage products of PLD6 are bound by either PIWIL1 (HIWI, MIWI) or PIWIL2 (HILI, MILI) in complexes with several other proteins. The 3' end is trimmed by an unknown exonuclease to generate the mature piRNA. PIWIL1:piRNA complexes appear to be involved in post-transcriptional silencing in the cytosol while PIWIL2:piRNA complexes generate further piRNAs from transposon transcripts and other transcripts in the cytosol. Cleavage products from PIWIL2:piRNA may be loaded into either PIWIL2 or PIWIL4 (HIWI2, MIWI2). Loading into PIWIL2 forms a step in a cytosolic amplification loop called the "ping-pong cycle" which yields further PIWIL2:piRNA complexes from cleaved precursor RNAs. Loading into PIWIL4 yields a complex also containing TDRD9 that translocates to the nucleus and directs DNA methylation of cognate loci, causing transcriptional silencing during spermatogenesis. Transcriptional silencing by piRNAs is necessary to limit transposition of endogenous transposons such as L1 elements in the genome.

Literature References
PubMed ID Title Journal Year
21427766 PIWI-interacting small RNAs: the vanguard of genome defence

Siomi, MC, Sato, K, Pezic, D, Aravin, AA

Nat. Rev. Mol. Cell Biol. 2011
22221002 piRNAs and their involvement in male germline development in mice

Pillai, RS, Chuma, S

Dev. Growth Differ. 2012
23124062 Biology of PIWI-interacting RNAs: new insights into biogenesis and function inside and outside of germlines

Ishizu, H, Siomi, H, Siomi, MC

Genes Dev. 2012
18282709 Conserved themes in small-RNA-mediated transposon control

Girard, A, Hannon, GJ

Trends Cell Biol. 2008
23829526 Piwi-interacting RNAs: biological functions and biogenesis

Sato, K, Siomi, MC

Essays Biochem. 2013
23980886 PIWI-interacting RNAs (piRNAs) - a mouse testis perspective

Bortvin, A

Biochemistry Mosc. 2013
23166399 piRNA and spermatogenesis in mice

Chuma, S, Nakano, T

Philos. Trans. R. Soc. Lond., B, Biol. Sci. 2013
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