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involved in the insulin-signaling pathway (
Hyun et al., 2009; Jin et al., 2012;
Varghese & Cohen, 2007; Varghese et al., 2010
). As mentioned above,
genetic analysis has shown that
miR-14
promotes fat metabolism and
developmental and adult viability by regulating
sugarbabe
and
EcR
expres-
sion, respectively (
Varghese & Cohen, 2007; Varghese et al., 2010
). Addi-
tional
miR-14
mutant phenotypes, including elevated apoptosis, could be
due to the misregulation of both
sugarbabe
and
EcR
or may involve addi-
tional unidentified
miR-14
targets. While current evidence suggests that
the 20E/
miR-14
/
sugarbabe
circuit may regulate ILPs to control adult pro-
cesses,
miR-8
integrates 20E and insulin signaling to control body size
during development (
Jin et al., 2012
). 20E signaling regulates pupal body
size, since feeding larvae a 20E-supplemented diet decreases animal size
while inactivating the 20E-receptor increases animal size (
Colombani
et al., 2003; Jin et al., 2012
). Consistent with the negative regulation of
miR-8
by 20E, ectopic expression of
miR-8
also leads to increased body
size. Genetic evidence indicates that 20E controls body size via
miR-8
,
since genetic depletion of
miR-8
suppresses the effects of 20E-receptor
knockdown. Likewise, the effects of ectopic 20E are genetically suppressed
by reduction in the
miR-8
target and negative regulator of insulin signal-
ing,
ush
. Thus, 20E represses
miR-8
levels to promote insulin signaling,
thereby modulating organismal growth rate.
4.6. miR-34
Despite its intriguing developmental profile and hormonally regulated
expression, a recent study showed that
D. melanogaster miR-34
plays an
important neuroprotective role in adults by regulating the Ecdysone induc-
ible developmental regulator,
Eip74ef
. This finding is consistent with previ-
ous genetics linking the miRNA pathway to long term brain integrity
(for review
Abe & Bonini, 2013
).
miR-34
is a brain-enriched miRNA
whose expression increases with age, possibly due to hormonal control
(
Liu et al., 2012
). Loss of function mutants of
miR-34
display premature
brain deterioration, early onset impaired motor behavior, altered chaperone
accumulation, reduced lifespan, and susceptibility to stress. While loss of
miR-34
triggered a transcriptional program seen during accelerated brain
aging, its upregulation extended median lifespan and mitigated neu-
rodegeneration induced by human pathogenic polyglutamine disease pro-
tein (
Liu et al., 2012
).
miR-34
and
Eip74ef
exhibit mutually exclusive
expression patterns in the aging adult brain, and age associated
mir-34
