Biology Reference
In-Depth Information
1. Introduction
MicroRNAs (miRNAs) are a class of small RNAs that are 20-24
nucleotides in length, and that function to regulate the expression of target
mRNAs (
Bartel, 2009
). This class of noncoding RNAs is well represented
in animal genomes and contains members that are perfectly conserved
between diverse species. The metazoan origin and evolutionary conserva-
tion of miRNAs indicate that they have essential roles in the biology of
multicellular animals (
Grimson
et al
., 2008
), and many display conserved
tissue-specific expression patterns (
Wienholds
et al
., 2005
). Consistent with
these expression profiles, miRNAs are known to play critical roles in diverse
cells and tissues during animal development (
Ambros, 2004
). This review
summarizes the current understanding of the roles that miRNAs play in
developing muscle. I concentrate on insights from the genetic analyses of
miRNA function in key model organisms including
Caenorhabditis elegans
,
Drosophila melanogaster
,
Danio rerio
, and
Mus musculus
, with apologies to
those whose work could not be included due to space constraints.
2. Muscle miRNA Regulatory Networks
The existence of muscle-specific miRNAs was suggested by one of
the first papers identifying miRNAs (
Lee and Ambros, 2001
). This paper
showed that the
miR-1
miRNA was highly expressed in human heart tissue
but not in human brain, liver, kidney, or lung tissue. Since then, the
expression of miRNAs in muscle has been studied intensively. This section
describes the identification of muscle miRNAs, as well as their placement
within genetic regulatory networks that control muscle formation and
function.
2.1. Identification of muscle miRNAs
Analysis of miRNA expression patterns in whole mount specimens was one
of the first approaches used to identify muscle miRNAs. Such analyses
found that
miR-1
is expressed specifically in muscles during the develop-
ment of worms (
Simon
et al
., 2008
), flies (
Kwon
et al
., 2005
;
Sokol and
Ambros, 2005
), zebrafish (
Wienholds
et al
., 2005
), and mice (
Zhao
et al
.,
2005
) and thus displays a striking evolutionary conservation of its tissue-
specific expression. Whole mount analysis identified numerous other miR-
NAs expressed in muscles, though most were expressed in other tissues as
well. These include
miR-45
,
-51
,
-90
,
-227
, and -
794
in
C. elegans
(
Martinez
et al
., 2008
),
miR-8
,
-13b-2
,
-184
, and -
316
in
D. melanogaster
