Biology Reference
In-Depth Information
in oogenesis in
dicer
mutants reflect a role for endo-siRNAs in the process (
Ma
et al
., 2010; Suh
et al
., 2010
). Consistently, expression profiles of Dicer mutant
oocytes revealed strong changes in the level of endo-siRNA-regulated tran-
scripts (
Murchison
et al
., 2007; Tang
et al
., 2007
).
3.3. endo-siRNA function in germ cell
differentiation—Spermatogenesis
The role of RNAi in spermatogenesis was first described in
C. elegans
where
mutants in the endo-siRNA pathway exhibited defects in this process (
Gent
et al
., 2009; Han
et al
., 2009; Ketting
et al
., 1999; Pavelec
et al
., 2009;
Rocheleau
et al
., 2008; She
et al
., 2009; Smardon
et al
., 2000; Tabara
et al
.,
1999
). Additionally, mutations affecting the biogenesis of the germline
specific 22G and 26G RNAs result in a range of defects in spermatogenesis
due to failure in chromosome segregation during mitosis and meiosis
(
Claycomb
et al
., 2009; Conine
et al
., 2010; Gu
et al
., 2009; Han
et al
.,
2009; van Wolfswinkel
et al
., 2009
).
The function of the 22G RNA in controlling mitosis could be related to
the finding that it recruits chromatin-modifying factors that promote local
histone modifications and establish perio-centromeric chromatin domains.
The subsequent binding and organization of factors crucial for proper mitotic
divisions such as Condensins or Cohesins allow proper chromosome segre-
gation (
Claycomb
et al
., 2009; Gu
et al
., 2009; van Wolfswinkel
et al
., 2009
).
The function of a subset of 26G endo-siRNAs loaded on the AGO proteins
ALG3 and ALG4 is essential for spermatogenesis by regulating gene expres-
sion during this process (
Conine
et al
., 2010; Han
et al
., 2009
).
Similar to the defects observed in oogenesis, male
dicer
mutant mice
display severe defects in germ cell proliferation and, subsequently, in sper-
matogenesis, but the relative contribution of miRNA and endo-siRNA
pathways is largely unknown (
Hayashi
et al
., 2008; Maatouk
et al
., 2008
).
4. piRNAs in Germ Cell Development
The Piwi protein was first identified in
D. melanogaster
where its
function is important for fertility. In the male fly, loss of Piwi function is
associated with severe defects in spermatogenesis giving the gene its name,
piwi
, for “P-element induced wimpy testis”
(Lin and Spradling, 1997)
.
Three mammalian Piwi homologues containing conserved PAZ and
PIWI domains were subsequently identified and shown to be required for
spermatogenesis as well (
Carmell
et al
., 2007; Deng and Lin, 2002;
Kuramochi-Miyagawa
et al
., 2001
).
