Small RNAs in Germ Cell Development - Current Topics in Developmental Biology - page 92

influence the secretion of steroid hormones in human primary granulosa cells
( Sirotkin et al ., 2010, 2009 ). Similarly, spermatogenesis is under tight control
of FSH and androgens, which regulate miRNA transcription level in sertoli
cells ( Nicholls et al ., 2011 ). Thus, hormones like LH and FSH can control the
transcription of specific miRNAs, which in turn are able to modulate output
levels of steroid hormones, thereby controlling gametogenesis.
3. Endogenous-siRNAs in Germ
Cell Development
RNAi was first demonstrated when C. elegans embryos were subjected
to exogenous dsRNAs ( Bernstein et al ., 2003; Fire et al ., 1998 ). The
introduced dsRNAs were cleaved by Dicer and loaded onto the siRISC
complex leading to degradation of a targeted gene. It was postulated that this
process constitutes a protective mechanism to counteract viral infections in
flies and reduce transposition activity in both C. elegans and D. melanogaster
( Bernstein et al ., 2003; Fire et al ., 1998 ). endo-siRNAs were first described
in plant and C. elegans ( Ambros et al ., 2003; Hamilton et al ., 2002 ) followed
by their identification in D. melanogaster and vertebrates ( Chung et al ., 2008;
Czech et al ., 2008; Ghildiyal et al ., 2008; Kawamura et al ., 2008; Okamura
et al ., 2008a,b; Zilberman et al ., 2003 ). The first mammalian endo-siRNA
was later characterized in cultured human cells where it regulates the L1
retrotransposon (Yang and Kazazian, 2006) . endo-siRNA expression in the
germline was detected by deep sequencing analysis performed on D. mela-
nogaster and mouse ovaries ( Tam et al ., 2008; Watanabe et al ., 2008 ).
3.1. endo-siRNA biogenesis and function
The endo-siRNAs are a class of 21-nt-short RNAs, present in both sense
and antisense orientations ( Czech et al ., 2008; Ghildiyal et al ., 2008;
Okamura et al ., 2008b ). The biogenesis of endo-siRNAs is reviewed in
detail in Ghildiyal and Zamore (2009), Ketting (2011), Kim et al . (2009) and
Okamura and Lai (2008) and is briefly described below.
endo-siRNA is derived from different templates including transposon
transcripts, heterochromatic sequences, sense-antisense transcript duplexes,
long stem loops, mRNAs, and from pseudogenes ( Chung et al ., 2008;
Czech et al ., 2008; Ghildiyal et al ., 2008; Sasidharan and Gerstein, 2008;
Tam et al ., 2008 ), which underlies their abundant expression. Considering
that transposons as well as endogenous gene sequences serve as templates for
endo-siRNA precursor synthesis, it became clear that their function is not
restricted to targeting and silencing transposons but rather extends to
regulation of gene expression ( Ghildiyal et al ., 2008; Okamura et al .,