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The small RNAs that interact and function in combination with the Piwi
proteins called piRNAs were shown to be expressed and function mainly in
the germline ( Aravin et al ., 2006; Girard et al ., 2006; Grivna et al ., 2006 ).
4.1. piRNA biogenesis and function
piRNAs are slightly larger than miRNAs (24-30nt as compared to 21-24nt)
and they are mapped to distinct, nonoverlapping clusters in the genome that
are often mapped to repeat sequences ( Aravin et al ., 2006; Houwing et al .,
2007 ). The mammalian piRNAs can be divided into two differentially
regulated subclasses of different sizes referred to as pachytene (29-31bp) and
pre-pachytene (26-28bp) piRNAs ( Aravin et al ., 2007b ). Pre-pachytene
piRNAs are expressed in spermatogonia prior to meiosis and become
depleted starting at mid-pachytene, while pachytene piRNAs are present in
spermatogonia around the pachytene stage of meiosis and are decreased when
the sperm reaches the haploid round spermatid stage. Whereas pachytene
piRNAs associate with the MIWI protein, pre-pachytene piRNAs preferen-
tially associate with MILI or MIWI-2. Functionally, pre-pachytene piRNAs
were suggested to control transposable elements as they are enriched with
genome repeat elements ( Aravin et al ., 2008, 2007b; Brennecke et al ., 2007 ),
while the biological role of pachytene piRNAs is not yet clear.
Two biogenesis pathways are responsible for piRNA biosynthesis: the
primary processing pathway and the secondary ping-pong amplification loop
( Fig. 4.2 C). First, the primary piRNA biogenesis pathway provides an initial
pool of piRNAs that target multiple transposable elements. Next, the ping-
pong cycle further shapes the piRNA population by amplifying sequences
that specifically target active transposons. These two pathways are conserved
in many animal species, including zebrafish ( Danio rerio ), frogs ( X. laevis ), fly
( D. melanogaster ), and mouse ( Brennecke et al ., 2007; Gunawardane et al .,
2007; Houwing et al ., 2007; Robine et al ., 2009; Vagin et al ., 2006 ). In
general, piRNAs are processed in a Dicer-independent manner ( Saito et al .,
2006; Vagin et al ., 2006 ); however, the mechanism of primary piRNA
production is not well understood. Nevertheless, studies in Drosophila
revealed that the RNA helicase Armitage, the putative nuclease Zucchini,
and Yb protein are involved in the primary pathway generating the piRNAs
(Saito and Siomi, 2010) . This pathway is thought to give rise to piRNAs that
are loaded onto Piwi/Aub (Aubergine, a Drosophila Piwi homologue) and is
the source for the pachytene piRNAs expressed in mammalian testis, which
are subsequently bound to MIWI and MILI ( Aravin et al ., 2006; Girard et al .,
2006; Grivna et al ., 2006; Lau et al ., 2006; Li et al ., 2009; Malone et al ., 2009;
Saito et al ., 2006; Watanabe et al ., 2006 ). The class I piRNAs produced by the
primary pathway are loaded onto Piwi/Aub and guide those proteins to their
transposon RNA targets. The Piwi-protein-mediated cleavage of the trans-
poson RNA target produces the class II piRNAs ( Brennecke et al ., 2007;
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