Biology Reference
In-Depth Information
phenotypes are suppressed by an
Eip74ef
hypomorphic allele. Although
miR-34
expression has been linked to aging and disease in higher eukaryotes,
the
miR-34
-
Eip74ef
relationship does not appear to be conserved (
Aw &
Cohen, 2012
). Thus, other mechanisms and targets may be involved in
mediating the age related
miR-34
function in these organisms. Determina-
tion of whether
miR-34
regulation of
Eip74ef
plays an important role during
developmental transitions awaits further investigation.
5. LIGHT MODULATED CIRCADIAN RHYTHM PATHWAYS
The physiology and behavior of many organisms are under the con-
trol of circadian rhythm (
Hall, 2003
). In
D. melanogaster,
the internal
clock receives external input and can be entrained by environmental
stimuli (
Dubruille & Emery, 2008
). The intrinsic clock synchronizes a
multitude of events, including adult eclosion time, rest/activity cycle, court-
ship, feeding, metabolism, and immune response (
Hall, 2003
). Studies
using
D. melanogaster
have provided deep molecular insights on how the
light/dark cycle feeds into the internal clock, how the intrinsic clock runs
on an approximately 24h rhythm, and also how the circadian clock regulates
the many physiological and behavioral outputs.
5.1. Molecular overview of circadian rhythm pathway
Transcriptional feedback loops are characteristic features of the circadian
clock, which include the central loop (CL) and interlocking loop (IL). In
the CL, expression of the heterodimeric activator complex composed of
clock (Clk) and cycle (Cyc) is transcriptionally repressed by its targets,
period
(
per
) and
timeless
(
tim
)(
Allada, White, So, Hall, & Rosbash, 1998; Hardin,
Hall, & Rosbash, 1990; Rutila et al., 1998; Sehgal, Price, Man, &
Young, 1994
). The IL stabilizes the CL, and therefore the circadian clock.
The components of the IL include the Par domain protein 1 (Pdp1), which
activates
clk
transcription, Vrille (Vri), which represses
clk
transcription, and
Clockwork Orange (Cwo), which represses Clk-mediated transcription
(
Hardin, 2005; Kadener, Stoleru, McDonald, Nawathean, & Rosbash,
2007
). In addition to transcriptional control, post-translational modifications
also regulate clock progression (
Chiu, Ko, & Edery, 2011; Yu, Zheng,
Houl, Dauwalder, &Hardin, 2006
). While the core transcriptional feedback
loops lead to rhythmic mRNA abundance, post-translational modification
such as ubiquitylation and phosphorylation controls circadian protein abun-
dance and sub-cellular location.
