Piwi gene was firstly cloned and characterized in Drosophila, and it showed that piwi is required
for the asymmetric division of germ-line stem cells. Piwi encodes a highly basic protein which is well conserved
A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal,Genes Dev.1998;
Girard, A. and Aravin, A. described a new class of small RNA that bind to MILI or MIWI(murine Piwi
protein) in mouse male germ cells, they referred to them as Piwi-interacting RNA(piRNA). piRNAs
are 26-31nt in length and share a strong preference for a 5’ uridine. Genomic mapping of piRNAs
reveals a limited number of clusters, wherein long stretches of piRNAs are derived from only one
strand. Similar piRNAs can also be found in rat and human, and the major clusters occurring in or-
thologous chromosomal regions.
A germline-specific class of small RNAs binds mammalian Piwi proteins,Nature 2006;442(7099):199-202
A novel class of small RNAs bind to MILI protein in mouse testes, Naure 2006;442(7099):203-207
Alexei A. Aravin discovered that the most abundant class of mouse prepachytene piRNAs are
generated from transposon-rich regions of the genome, it suggested that piRNAs function in
Developmentally regulated piRNA clusters implicate MILI in transposon control, Science 2007;316(5828):744-747
Mice lacking one or more of their piwi homologs were found to have substantial demethylation and
derepression of transposable elements, it pointed toward a role for piRNAs in maintaining germline
genome integrity and transposon control throught de novo DNA methylation.
A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol. Cell 2008;31(6), 785–799
An epigenetic role for maternally inherited piRNAs in transposon silencing. Science 2008;322(5906), 1387–1392
DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes
Dev. 2008;22(7), 908–917
it has been discovered that a few piRNA derive from individual mRNA transcripts, and could participate
in ping-pong mechanism to generate secondary piRNAs.
A single female-specific piRNA is the primary determiner of sex in the silkworm Nature 2014;509:633-636
Priyamvada found piRNA have a critical role in the epigenetic regulation of CREB2 promoter.Expos-
ure to serotonin causes a significant but delayed upregulation of the neuronally enriched piRNA piR-F,
which recruits the piwi/piRNA complex to bind a target site on the nascent transcript in the 5'UTR of
CREB2 pre-mRNA by putative sequence-specific direction. This leads to the recruitment of factors that
promote the activation of DNMT, a DNA methyltransferase. DNMT acts to methylate the proximal (but
not the distal) CpG island in the CREB2 promoter, leading to reduced expression of CREB2, induction of
long-term facilitation, and formation of memory.
A Role for Neuronal piRNAs in the Epigenetic Control of Memory-Related Synaptic Plasticity Cell 2008;149(3):694-707
Dubravka Pezic found transcripts from a full-length LINE in the nucleus of embryonic prospermatogonia
are recognized by a MIWI2–piRNA complex, which recruits a histone methyltransferase (HMTase). This
results in deposition of the H3K9me3 mark on LINE 5’repeats and in the adjacent upstream region. The
piRNA associates only with transcripts from actively transcribed copies of TEs. Truncated copies, which
are not transcribed, are not targeted by piRNAs.
piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells Genes & Development