Biology Reference
In-Depth Information
2009
). Last, Hu proteins were recently shown to relieve “germline
mRNAs” from miRNA repression in
Xenopus
(
Koebernick
et al
., 2010
).
These results suggest that multiple proteins cooperate to ensure the expres-
sion of such mRNAs in the germline despite the presence of miRNAs in
the same cells.
Considering that similar mechanisms control this process in
C. elegans
,
D. melanogaster
, and
X. laevis
, the role for miRNAs in promoting clearance
of maternally provided transcripts in somatic cells appears to be conserved
(
Bushati
et al
., 2008; Lund
et al
., 2009; Wu
et al
., 2010
). Interestingly, as
discussed below, mRNA decay during maternal-to-zygotic transition can
also be directed by another group of small RNA molecules, the piRNAs, as
shown for
nanos
mRNA (
Rouget
et al
., 2010
).
In contrast to germline specification by maternally provided germ plasm
described above, in other organisms such as mouse and Urodele amphi-
bians, the germline is specified by inductive signals produced by the embryo
itself (
Boterenbrood and Nieuwkoop, 1973; Nieuwkoop, 1947; Tam and
Zhou, 1996; Tsang
et al
., 2001
).
Two key factors involved in mouse PGC specification are the transcrip-
tion regulators PRDM1 (also known as BLIMP1) and PRDM14 that are
expressed at embryonic day E6.25 in the region where the PGCs arise
(
Fig. 4.1
C(a)). The expression of PRDM1 and PRDM14 is induced by
BMPs, and loss-of-function experiments revealed the critical role they play
in PGC specification (
Ohinata
et al
., 2005; Robertson
et al
., 2007; Vincent
et al
., 2005; Yamaji
et al
., 2008
). Persistent expression of both proteins in the
germline allows PGC development by repression of genes characteristic of
somatic differentiation (e.g.,
Hox
genes). Additionally, PRDM14 functions
as a key regulator for the reacquisition of pluripotency and genome-wide
epigenetic reprogramming (
Kurimoto
et al
., 2008; Vincent
et al
., 2005
).
Whereas the function of PRDM1 is essential for additional processes in
embryogenesis, embryos lacking PRDM14 function are viable but infertile
(
Kurimoto
et al
., 2008; Vincent
et al
., 2005
), suggesting a specific role in
germline development for the latter.
Following the induction by BMP, PRDM14 expression is maintained by
PRDM1 (
Yamaji
et al
., 2008
), and continued regulation over the extent of
PRDM1 expression is important. Interestingly, as originally identified in the
context of Hodgkin's lymphoma, PRDM1 is suppressed by the miRNA
let-
7
, which targets a miRNA seed within the 3
0
UTR of the
prdm1
mRNA
(
Nie
et al
., 2008
). This regulation calls for a mechanism relieving
let-7
-
mediated inhibition in the developing germline. The mechanism involves
LIN-28, a translational regulator first identified in
C. elegans
(Ambros, 1989)
,
that was shown to modulate
let-7
activity by direct binding to the precursor
of
let-7
miRNA (pre-
let-7
)(
Newman
et al
., 2008; Piskounova
et al
., 2008;
Rybak
et al
., 2008; Viswanathan
et al
., 2008
). In this case, LIN-28 induces
uridylation at the 3
0
end of the pre-miRNA by recruiting the noncanonical
