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certain subcellular vesicles, and this could impact repression by miRNAs.
Subcellular structures such as P-bodies and stress granules have been identi-
fied as sites at which miRNAs accumulate, but their roles in miRNA
biology remain obscure (
Leung
et al
., 2006
;
Pontes and Pikaard, 2008
).
Taken together, miRNA binding sites within a 3
0
UTR appear to be
subjected to a variety of regulatory mechanisms, and this is reminiscent of
the diverse ways in which promoter regions upstream of genes are used to
control transcription.
4. MicroRNAs Regulate Different Stages
of Hematopoiesis
A plethora of recent reports indicate that miRNAs are essential for
proper hematopoietic development and act at various points throughout the
process, from HSCs through terminal differentiation (
O'Connell
et al
.,
2010c
). It is also becoming clear that miRNAs can have both positive and
negative impacts on specific aspects of developing blood cells, indicating
that their functions must be properly integrated to ensure blood cell
homeostasis (
Fig. 6.2
A).
4.1. Hematopoietic stem cells
Mammalian hematopoiesis is a hierarchical developmental system that
depends upon a rare stem cell population to ensure production of blood
cells throughout the lifetime of an individual (
Orkin and Zon, 2008
).
Because HSCs are long lived and must strike a careful balance between
differentiation and self-renewal, they are good candidates to be regulated by
miRNAs. In fact, a number of reports have linked miRNAs to proper HSC
function (
Guo
et al
., 2010
;
O'Connell
et al
., 2010a
;
Ooi
et al
., 2010
).
Inducible deletion of Dicer or Ars2, involved in miRNA processing, con-
ferred a competitive disadvantage on engrafting HSCs and overall hemato-
poiesis (
Gruber
et al
., 2009
;
Guo
et al
., 2010
). This reduction in fitness in the
absence of miRNAs could be a consequence of many different aspects of
stem cell biology. Stem cell maintenance and function involve many cellular
processes including apoptosis, proliferation, differentiation, and cellular
trafficking. Specific miRNAs have started to be linked to these events.
For instance, the miR-125 family is enriched in HSCs and has been
shown to target genes involved in apoptosis (
Guo
et al
., 2010
;
Ooi
et al
.,
2010
). miR-196b is also expressed in HSCs (
O'Connell
et al
., 2010a
;
Popovic
et al
., 2009
) and regulates specific Hox family members that control
differentiation (
Yekta
et al
., 2004
). The mechanisms underlying the HSC
choice between self-renewal and differentiation remain to be clearly
