Biology Reference
In-Depth Information
5.2. Identification of miRNAs in clock pathways
Post-transcriptional control also likely regulates the circadian clock, and
recent analysis identified a set of miRNAs that may be involved (see
Fig. 4.3
). A microarray study, for example, detected two mature miRNAs
miR-263a
and
miR-263b
that display a circadian expression profile in adult
heads (
Yang, Lee, Padgett, & Edery, 2008
). This study also identified
miRNAs whose expression profile is altered in
cyc
mutants, including
miR-31a, miR-124, miR-133, miR-184, miR-210
, and
miR-276b
. In a sep-
arate study, tiling array analysis of adult heads similarly identified a set of pri-
miRNA transcripts whose expression increases when Dicer processing is
disrupted specifically in circadian neurons. These include primary transcripts
encoding
bantam
,
let-7-Complex
miRNAs,
miR-8
,
miR-9a
,
miR-14
,
miR-12
,
miR-34
,
miR-184
,
miR-252
,
miR-263a
,
miR-274
,
miR-275, miR-276a
,
miR-277
,
miR-278
,
miR-279, miR-282
,
miR-283
,
miR-284
,
miR-285
,
miR-286a
,
miR-304, miR-305, miR-317, miR-986
, and
miR-996
(
Kadener, Menet, et al., 2009
). Disruption of additional miRNA processing
components, like Drosha, leads to elevation of a subset of these, including
pri-bantam
. MiRNAs are present in circadian neurons and may regulate the
stability or translation of core clock components
clk
,
vri
, and
cwo,
since these
mRNAs are enriched in immunoprecipitations of the RISC component
Ago-1 from fly heads harvested at specific times (
Kadener, Menet, et al.,
2009
). Such identification of circadian miRNAs is consistent with compu-
tational simulations suggesting that miRNAs can alter both the amplitude and
frequency/periodicity of circadian oscillations (
Nandi, Vaz, Bhattacharya, &
Ramaswamy, 2009
). Genetic analyses have already illuminated a role for
bantam
,
miR-279
, and the
miR-959-964
cluster miRNAs, andwe review this
evidence below.
5.3. bantam
While
bantam
does not exhibit a circadian pattern of expression at the organ-
ismal level (
Vodala et al., 2012
), its expression may cycle in adult circadian
neurons. A role for
bantam
within the central clock is suggested by the pres-
ence of a binding site for this miRNA in the 3'UTR of
clk
(
Kadener, Menet,
et al., 2009
). Rescue experiments indicate the importance of this site, since it
is required in a
clk
rescuing transgene to restore rhythmicity to an arrhythmic
clk
mutant. Consistent with a role in regulating Clk, overexpression of
bantam
leads to significantly longer period rhythms. Detailed analysis of bantam's
clock function is challenging due to its essential function during develop-
ment, and awaits its specific removal in adult circadian neurons.
