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Daphnia,
and is located between
abd-A
and
Abd-B
in all cases (
Fig. 2.1
)
(
Aravin
et al
., 2003
;
Miura
et al
., 2011
;
Ronshaugen
et al
., 2005
). Both
miRNAs show perfect conservation in the 5p and 3p seed sequences across
all arthropods, and near-perfect conservation for all four mature transcripts
(
Miura
et al
., 2011
;
Ronshaugen
et al
., 2005
).
2.2.4.
miR-615
miR-615
is found only in eutherian mammals, in a single copy located
within the second intron of
Hoxc-5
.
miR-615
may be processed from the
major
Hoxc-5
transcript, as EST libraries do not suggest any additional
transcript structures or alternative promoters (
Kent, 2002
). Mature
miR-
615
transcripts processed from both arms of the pre-miRNA have been
recovered, and transcripts have been isolated from multiple tissues, but to
date no function for this miRNA has been reported (
Chiang
et al
., 2010
;
Landgraf
et al
., 2007
;
Mineno
et al
., 2006
).
3. Predicted Targets of Hox-Embedded miRNAs:
A Role in Posterior Prevalence, and More?
While miRNAs located within Hox clusters are predicted to target
hundreds of mRNA transcripts, a striking bias toward targeting Hox genes
themselves has been identified (
Woltering and Durston, 2008
;
Yekta
et al
.,
2004, 2008
). Moreover, the potential scale of this regulation is quite
extensive with individual Hox 3
0
UTRs having up to four (
Hoxa-7
,
Hoxc-
8
in vertebrates) or even seven (
Ubx
in
Drosophila
) target binding sites. This
statistical enrichment of Hox targets becomes even more intriguing when
the asymmetric distribution of these targets is considered (
Woltering and
Durston, 2008
;
Yekta
et al
., 2008
). Predicted targets of Hox-embedded
miRNAs are, in general, located genomically adjacent to but more 3
0
(proximal) in the cluster than the miRNA (see
Table 2.1
). This is clearly
exemplified by
miR-196
in
Mus musculus
where target sites for these miR-
NAs have evolved in 10 nearby Hox genes, all positioned more 3
0
and
expressed more anteriorly. This bias largely holds true for
miR-iab4/8
in
Drosophila
and for most of
miR-10
targets in vertebrates as well, although
some targets do not follow this trend. In
Drosophila
, all
miR-10
targets are
instead located genomically more 5
0
(distal) though whether genomic
positioning in this context strictly translates to more posterior developmen-
tal expression will be discussed in
Section 4.2.1
. This analysis is restricted to
the 3
0
UTR, where evolutionary conservation within a rapidly diverging
region is important in identifying
bona fide
target sites. However, coding
sequence may also represent a valid target
for miRNA regulation
(
Woltering and Durston, 2008
).