Biology Reference
In-Depth Information
(
Aboobaker
et al
., 2005
), and
miR-133
,
-206
,
-216,
and -
499
in zebrafish
(
Kloosterman
et al
., 2006
;
Wienholds
et al
., 2005
).
Microarray analysis and deep sequencing experiments have significantly
extended the number of miRNAs implicated in vertebrate muscle develop-
ment. These expression-profiling approaches have focused on identifying
the complete repertoire of muscle miRNAs in embryonic and adult muscle
tissue from diverse species (
Huang
et al
., 2008
;
Li
et al
., 2011
). Microarray
analysis of mouse tissue, for example, identified a total of 114 miRNAs that
are expressed in the mouse heart, 25 of which are apparently heart specific
(
Tang
et al
., 2007
). Subsequent deep sequencing of young adult mouse heart
tissue found an enrichment of a small number of miRNAs, with
miR-1
accounting for 40% of all cardiac miRNA expression (
Rao
et al
., 2009
). The
level of
miR-1
expression is striking:
miR-1
is
20-fold more abundant than
miR-208
, a miRNA encoded within the intron of a cardiac myosin and
therefore a reasonable proxy for a highly expressed cardiac mRNA. Other
miRNAs enriched in heart tissues include members of the
let-7
,
miR-26
,
miR-29
, and
miR-30
families.
In a parallel approach to identify miRNAs involved in muscle biology,
miRNA expression dynamics have been profiled in cultured mammalian cells
undergoing skeletal or cardiac muscle differentiation (
Chen
et al
., 2006
;
Dey
et al
., 2011
;
Ivey
et al
., 2008
;
Naguibneva
et al
., 2006
). For example, the
expression of a collection of miRNAs including
miR-1
,
-22
,
-26
,
-133
,
-181
,
-206
,and
-486
is upregulated as cultured murine C2C12 myoblasts differenti-
ate into skeletal muscle (
Chen
et al
., 2006
;
Dey
et al
., 2011
;
Naguibneva
et al
.,
2006
). Activation of these miRNAs may be required to promote differentia-
tion programs and is coincident with the downregulation of a second set of
C2C12-expressedmiRNAs including
miR-125b
(
Ge
et al
., 2011
), which likely
repress C2C12 differentiation. Indeed, an analogous role for
miR-125b
has
recently been found during skin cell differentiation, since
miR-125b
is highly
expressed in skin progenitor cells and is sharply downregulated during their
differentiation (
Zhang
et al
., 2011
).
Similar profiling approaches have also been used to identify miRNAs
involved in cardiac muscle differentiation. For example, 17 murine miR-
NAs are upregulated as embryonic stem cells differentiate into cardiomyo-
cytes, including
miR-1
,
-133
,
-143
,
-182
,
-200
, and -
295
(
Ivey
et al
., 2008
).
Taken together, these profiling analyses indicate that muscles have a rich
palette of miRNAs that likely play myriad diverse roles during muscle
development.
2.2. Genomic organization of muscle miRNAs
In many animal genomes, muscle miRNAs are found clustered together
(see
Fig. 3.1
). In both the mouse and human genomes, for example, each of
the three members of the
miR-1
family of miRNAs is located next to a
