Biology Reference
In-Depth Information
results in small flies with defective insulin signaling. Fat body specific expres-
sion of
miR-8
restores body size and weight to near
wild type
levels. Both
miR-8
and its mammalian ortholog,
miR-200
, activate phosphatidylinositol
3-kinase (PI3K) by repressing the expression of
u-shaped (ush)
and
fog2
,respec-
tively. Ush and Fog2 are orthologous proteins that interact directly with the
regulatory subunits of PI3K and inhibit the formation of an active PI3K com-
plex. Thus
,miR-8
can activate insulin signaling by suppressing
ush
, leading to
the cell-autonomous growth of fat body as well as non-autonomous systemic
growth of the organism (
Hyun et al., 2009
).
3.6. miR-33
Gain-of-function studies implicated
miR-33
in maintenance of lipid homeo-
stasis in
D. melanogaster
(
Davalos et al., 2011
). Like its mammalian counterpart
miR-33a
,fly
miR-33
is located in the intron of
Sterol regulatory element-binding
protein
(
Srebp
), a gene involved in fatty acid metabolism. Forced expression
of
miR-33
in the fat body resulted in increased levels of triacylglycerols
upon starvation as well as abnormal lipid accumulation. These phenotypes
are consistent with inappropriate repression of the
miR-33
target
withered
,
a mitochondrial enzyme that
regulates
fatty acid oxidation (
Davalos
et al., 2011
).
3.7. dcr-1
The IIS signaling pathway has also been shown to regulate cell division in
germline stem cells (GSCs) in a miRNA dependent manner (
Yu et al.,
2009
). This regulation is dependent on the cyclin dependent kinase inhibitor
and p21/p27 homolog, Dacapo (Dap) as the cell cycle defects of
InR
-
deficient GSCs were partially rescued by a reduction in
dap
. Moreover,
genetic as well as cell cycle analyses of Dicer-1 have highlighted the impor-
tance of the miRNA pathway in GSC maintenance and division. GSCs
mutant for
dcr-1
displayed a Dap dependent reduction in germline cyst pro-
duction and a defective cell cycle control (
Hatfield et al., 2005
). Subsequent
work by Yu et al., has shown that the
dap
3'UTR harbors binding sites for
miR-7
,
miR-278
, and
miR-309
. Although GSCs mutant for
miR-7
and
miR-278
displayed cell cycle defects, none of these defects were as dramatic
as
dcr-1
mutant GSCs, thus implicating other unidentified miRNAs in this
pathway (
Yu et al., 2009
). Thus, both Dicer 1 and Dap function in a nutrient
dependent manner to regulate GSC homeostasis.
