Biology Reference
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Gunawardane
et al
., 2007
), which are loaded onto Ago3. The Ago3/piRNA
complex then targets the transcripts of piRNA cluster to generate more
antisense piRNAs that are loaded onto PIWI/Aub, thus amplifying the
pool of piRNAs targeting transposons (
Fig. 4.2
C).
The two biosynthetic pathways described above have been identified in all
model organisms, while in
C. elegans
, a third group of Piwi-binding small
RNAs was identified, the 21U-RNAs (
Ruby
et al
., 2006
). These RNAs are
smaller than other piRNAs and are synthesized by a different pathway and
function in transposon silencing as well (
Batista
et al
., 2008; Ruby
et al
., 2006;
Wang and Reinke, 2008
). For detailed reviews on piRNA biogenesis, see
Ghildiyal and Zamore (2009), Ketting (2011), Lau, 2010 and Siomi
et al
.
(2011)
.
As many steps in piRNA biogenesis still remain elusive, further inves-
tigations of the details of their maturation and function would help to better
understand how piRNAs can effectively guard the germline genome against
transposable elements.
4.1.1. piRNAs defend against transposable element activity
As mentioned above, piRNAs can recognize and destroy transposable ele-
ment transcripts derived from multiple sites that are spread throughout the
genome. The importance of the piRNA pathway and specifically the ampli-
fication loop in defending the genome against excessive transposon mobili-
zation was demonstrated in studies involving crosses between different
Drosophila
strains (
Brennecke
et al
., 2008
). Such crosses can produce sterile
progeny through the phenomenon called “hybrid dysgenesis”. The basis for
this phenomenon is the lack of maternally provided piRNAs that target
transposons carried by the paternal genome (
Bourc'his and Voinnet, 2010;
Brennecke
et al
., 2008
). In other crosses between the same strains, maternal
deposition of piRNAs into the egg provides the embryo with an initial
piRNA pool to launch the amplification cycle for effective defense against
DNA damage caused by transposon mobilization. Similarly, knockout of
two members of the mouse PIWI-protein family,
mili
and
miwi-2
, but not
miwi
, leads to the activation of retrotransposons in the male mouse germline,
gametogenesis arrest, and consequently to complete sterility in males (
Aravin
et al
., 2007b; Carmell
et al
., 2007; Kuramochi-Miyagawa
et al
., 2008
).
Similarly, Zebrafish bearing mutations in the Piwi proteins, Ziwi and Zili,
show derepression of transposable elements and male sterility.
Interestingly, CpGDNAmethylation, which functions in transcriptional
silencing of LINE and LTR retrotransposons in the genome, is decreased in
the male germline of
mili
and
miwi-2
mutants (
Aravin
et al
., 2007b;
Kuramochi-Miyagawa
et al
., 2008
). It was thus hypothesized that the piR-
ISC (piRNA induced silencing complex) can also guide the
de novo
methyl-
ation machinery to loci of transposable elements, and consistently MIWI-
2 protein loaded with antitransposon piRNAs is present in the embryo at the
