Biology Reference
In-Depth Information
Table 2.1
Predicted targets of Hox-embedded miRNAs in
Drosophila
and mouse
Drosophila
Mus musculus
miR-10-5p
miR-10-3p
miR-10
Scr
Ubx, Abd-B
Hoxa1, Hoxa3, Hoxb3, Hoxd1
Hoxd10
mir-196
mir-iab-4/miR-iab-8
Scr,
Antp
, Ubx, abd-A
Hoxa4, Hoxa5, Hoxa7, Hoxa9,
Hoxb1, Hoxb6, Hoxb7, Hoxb8,
Hoxc8, Hoxd8
AbdB
Gray shade indicates whether target genes are genomically located more 3
0
(light gray) or 5
0
(dark gray) in
the cluster than the miRNA.
The relative genomic positioning of Hox miRNAs and their targets has
important implications for predicting their patterns of coexpression and func-
tional interactions. Colinear Hox transcription results in staggered yet over-
lapping expression of adjacent genes, with each vertebral segment inmammals,
for example, normally requiring input from at least two paralog groups
(
McIntyre
et al
., 2007
; reviewed in
Wellik, 2007
). The evolution of miRNA
target sites in adjacent or near-adjacent genes allows at least the possibility that a
miRNA is coexpressed with its target genes, where it may act as a tuning
mechanism to optimize functional output (
Fig. 2.2
). Dependent on their
relative expression levels at the posterior boundary of target Hox expression,
this could essentially abolish functional output of the target mRNA, thereby
sharpening boundary formation. In addition, positioning of the miRNA 5
0
to
its targets suggests that its expression will also extend more posteriorly than its
targets, where it could act as a failsafe mechanism to repress aberrant Hox
transcripts posterior to their domains (
Fig. 2.2
). This latter role would be
expected to reinforce the phenomenon of posterior prevalence, whereby
genes located more posteriorly exert a phenotypic dominance over more
anterior programs. Indeed, although still poorly understood, posttranscrip-
tional control is known to contribute to posterior prevalence (
Gehring
et al
.,
2009
). Experimental evidence exists for both tuning and failsafemechanisms of
miRNA-Hox interaction (
Asli and Kessel, 2010
;
Hornstein
et al
., 2005
;
McGlinn
et al
., 2009
), and understanding the relative contribution of each to
a given developmental systemwill require detailed characterization of the level
of coexpression between the miRNA and its target genes.
