Biology Reference
In-Depth Information
3.2. Identification of miRNAs involved in insulin signaling
Over the past several years, miRNAs have been identified as key post-
transcriptional players in the regulation of metabolic processes in response
to environmental fluctuations (
Krutzfeldt & Stoffel, 2006
). Here, we discuss
the roles of
D. melanogaster
miRNAs that impinge on insulin signaling and
nutritional pathways
. D. melanogaster
miRNAs implicated in homeostasis
include
miR-14
,
mir-278
,
miR-8
,
miR-33
, and
miR-1
(see
Fig. 4.1
).
3.3. miR-14
miR-14
was the first
D. melanogaster
miRNA implicated in metabolism. It
was initially identified in a forward genetic screen for mutants that suppress
apoptotic cell death (
Xu, Vernooy, Guo, & Hay, 2003
).
miR-14
mutants
display a series of phenotypes, including reduced viability during develop-
ment, reduced lifespan, elevated apoptosis, increased stress response, and
increased diacylglycerol and triacylglycerol levels. This
miR-14
mutant fat
metabolism defect leads to an obese phenotype, whereas extra copies of
miR-14
lead to lean flies (
Xu et al., 2003
). These metabolic phenotypes were
attributed to a reduction in the expression of ILPs, since
miR-14
functions in
the IPCs to regulate expression of a nutrient sensitive regulator of
dilp
expression,
sugarbabe
(
Varghese, Lim, & Cohen, 2010
). While
miR-14
per-
forms its metabolic function by regulating
sugarbabe
, it also ensures viability
during development and adulthood by regulating the expression of other
mRNA targets including
Ecdysone Receptor
(
EcR
), as discussed below.
3.4. miR-278
miR-278
was originally identified in a genetic screen for genes whose forced
expression causes robust overgrowth.
miR-278
mutants display a lean phe-
notype that is attributed to increased expression of ILPs (
Teleman, Maitra, &
Cohen, 2006
). Moreover, elevation of insulin levels in
miR-278
mutants is
unable to renormalize the increased circulating sugar levels in the organism.
Overexpression of the
miR-278
target mRNA
expanded
in the fat body is
sufficient to phenocopy this decreased insulin sensitivity (
Teleman et al.,
2006
), suggesting that the main function of
miR-278
is to suppress expres-
sion of this single target mRNA in fat body cells.
3.5. miR-8
miR-8
is another miRNA that functions in the fat body to regulate organismal
growth and metabolism (
Hyun et al., 2009
). Genetic elimination of
miR-8
