Biology Reference
In-Depth Information
These include the pathways regulated by small peptide hormones, like insu-
lin, as well as pathways regulated by lipohilic hormones, like ecdysteroids
and juvenile hormones. We also consider the role of miRNAs in other
pathways that coordinate cell behaviors throughout the animal and in
response to environmental cues, including circadian rhythm, stress, and
immune response pathways.
2. OVERVIEW OF miRNA BIOGENESIS AND FUNCTION
Mature miRNAs are derived from longer transcripts via two cleavage
steps (for a review of miRNA biology, see
Krol, Loedige, & Filipowicz,
2010
). The first cleavage involves the RNAse III-domain containing enzyme
Drosha, which releases a
70-nt hairpin structure from a longer primary
miRNA (pri-miRNA) transcript. This hairpin is exported to the cytoplasm,
where a second endoribonuclease, Dicer (Dcr), executes the next cleavage
that releases the mature miRNA. Emerging evidence indicates that this
post-transcriptional processing of miRNAs is highly regulated by a host of
additional regulatory molecules (
Siomi & Siomi, 2010
). Once released, the
mature miRNA enters the RNA-induced silencing complex (RISC)
complex, which contains members of the Argonaute (Ago) family of proteins,
and binds to target mRNAs, leading either to their translational repression or
degradation. The precise mechanisms of miRNA-mediated gene silencing as
well as the full repertoire of responsible cofactors remain to be identified.
3. INSULIN AND NUTRITIONAL PATHWAYS
An indispensable function of all living cells is to control the rates of
metabolic processes in response to changes in the environment. The nutri-
tional status of an organism is reflected by the levels of insulin, which in turn
maintains a balance between circulating sugars and stored resources such as
glycogen and fats. Another key role played by the insulin pathway is the con-
trol of cellular and organismal growth. Genetic manipulation of a number of
components in this pathway in
Drosophila
has highlighted the role of insulin
signaling in regulation of body size (
Broughton et al., 2005; Rulifson,
Kim, & Nusse, 2002
). In this section, we first describe the molecular frame-
work of the insulin-signaling pathway in
D. melanogaster
and then discuss the
role of recently identified miRNAs in this pathway.
