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switching (
Griffiths-Jones
et al
., 2011
). miR
-933
similarly exhibits arm
switching (
Griffiths-Jones
et al
., 2011
;
Marco
et al
., 2010
). Second,
miR-
10
transcripts are subject to both RNA editing and seed shifting, documen-
ted in cephalochordates (which also show an unusual pattern of
miR-10
gene duplication;
Fig. 2.1
), echinoderms, insects, and a priapulid (lopho-
trochozoan) (
Marco
et al
., 2010
;
Wheeler
et al
., 2009
). Seed shifting allows
multiple miRNAs to be processed from one primary transcript by varying
the position of the 5
0
end of the mature miRNA. All of these modifications
alter the predicted targeting specificity of processed transcripts.
miR-10
has
not been functionally characterized outside of vertebrates, so the signifi-
cance of alternative processing is unknown.
4.2. Developmental expression, target predictions,
and function
4.2.1.
Drosophila miR-10
In
Drosophila
,
miR-10
expression initiates at the cellular blastoderm stage, in
a striped pattern within central segments. It is downregulated during gas-
trulation but reinitiates throughout the ventral nerve cord and in the
posterior midgut and hindgut (
Aboobaker
et al
., 2005
).
Drosophila miR-10
is predicted to regulate several Hox mRNAs, and the
miR-10-
5p and -3p
transcripts have different predicted targets (
Table 2.1
). A strong, compensa-
tory
miR-10-5p
site is predicted in the 3
0
UTR of
Scr
(a
Hox5
ortholog) that
is conserved across
Drosophilids
and present in other insect orders
(
Brennecke
et al
., 2005
;
Enright
et al
., 2003
;
Miura
et al
., 2011
).
miR-10-
3p
(the predominant product in
Drosophila
but not in other insect orders;
Griffiths-Jones
et al
., 2011
) is predicted to bind the
Ubx
and
Abd-B 3
0
UTRs
via sites conserved across
Drosophilids
(
Stark
et al
., 2007
)
.
None of these
potential interactions has been tested but predicted targeting of more distal
genes within the cluster stands in contrast to vertebrates, where
miR-10
primarily targets
Hox1-3
genes (reviewed in
Yekta
et al
., 2008
). However,
at least for
Scr
(but not other targets),
Drosophila miR-10
expression actually
extends further posteriorly. The
miR-10
primary transcript is expressed
throughout central segments, but
Scr
is restricted to parasegments 2-3
(precursors of maxillary, labial, and T1 segments) (
Aboobaker
et al
., 2005
;
Kuroiwa
et al
., 1985
;
Riley
et al
., 1987
). Thus, despite their genomic
positions, this interaction appears to follow the trend of targeting more
anteriorly expressed genes.
4.2.2.
C. elegans miR-57
Although
C. elegans
lacks clustered Hox genes,
miR-57
is expressed in a
Hox-like, axially restricted pattern, initiating in the posterior embryo in
cells of diverse lineages. Expression persists in larvae and adults (
Zhao
et al
.,
2010
).
