MicroRNAs as Components of Systemic Signaling Pathways in Drosophila melanogaster - Current Topics in Developmental Biology - page 115

expression pattern, genetic elimination of miR-279 leads to an arrhythmic
activity cycle. RNAi knockdown studies of predicted miR-279 targets iden-
tified a bona fide target, Unpaired (Upd), the JAK-STAT pathway secreted
ligand. The upd 3'UTR contains mir-279 responsive binding sites. Flies in
which upd is knocked down also exhibit impaired locomotor rhythm,
suggesting the requirement of the JAK-STAT pathway for normal rhythm.
It turns out that altering the levels of other JAK-STAT pathway components
(Hop, Dome) also disrupted locomotor rhythm. MiR-279 is detected in
neurons that can receive direct input from circadian neurons in their imme-
diate proximity. These cells also express Upd, whose expression miR-279
regulates. This modulation of Upd regulates the oscillating rest: activity
cycle via circadian STAT92E output ( Luo & Sehgal, 2012 ).

5.5. miR-959 964 cluster

The miR-959-964 cluster represents another example of miRNAs involved
in the circadian output. MiRNAs encoded by this cluster have short half-
lives and display a circadian expression that peaks at dusk (ZT12) and has
its lowest level at dawn (ZT0) ( Vodala et al., 2012; Yang et al., 2008 ).
The pri - miR-959 - 964 transcript also cycles, suggesting the involvement of
the circadian transcription control on the locus. In fact, clk mutants abolished
the circadian expression of the cluster miRNAs. Transcription of the cluster
is also regulated by nutritional status, since feeding activates transcription
of the cluster while starvation represses cluster transcription. Analysis of a
mutant that eliminates four of the six miRNAs revealed many roles in cir-
cadian governed behavior, feeding and metabolism. Elimination of the clus-
ter reduces the period by half an hour, while cluster over-expression mutants
extend the period by an hour. Low levels of cluster miRNAs correlate with
feeding time. Gradual increase in miRNA cluster expression prepares the
animal for normal physiology post-feeding, until the cluster miRNAs begin
to decay and reach their trough levels in the morning. The targets of these
miRNAs remain to be determined.

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6. STRESS INDUCED AND IMMUNE RESPONSE
PATHWAYS
Innate immunity in flies arises from a number of immune-responsive
tissues which are capable of sensing pathogen and mount a defensive reaction
( Lemaitre & Hoffmann, 2007 ). The epithelial layer underneath the body
cuticle, in the intestinal tract acts as a physical barrier against infection. This