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| 2 | 2011
Klinisk Biokemi i Norden
MicroRNAs (miRNAs) are a new class of small,
endogenous, non-coding RNA molecules with
functional properties (1). Several studies have
shown miRNAs to play key regulatory roles in
a variety of essential biological processes, inclu-
ding development, metabolism, cell- prolifera-
tion, differentiation and death, as well as in dif-
ferent diseases (2). The regulatory properties are
exerted on their specific targets, the messenger
RNAs (mRNAs), thereby controlling gene expres-
sion mainly by translational inhibition or degra-
dation of the mRNA. miRNAs have been detected
in almost all higher eukaryotes, and their evolu-
tionary conservation across different species cor-
roborates their functional importance.
The discovery of miRNAs as posttranscriptional regu-
lators has added yet another layer of complexity to the
mechanisms that govern basal and disease-directed
gene expression. The discovery of miRNA has trig-
gered an explosion of research activities, but has left
many unanswered questions about how this regulation
MicroRNA: Key regulators of gene expression
-
analytical aspects and clinical potential
Helge Røsjø
1,2,3
,
Kari Bente Foss Haug
4
1
Division of Medicine, Akershus University Hospital, Lørenskog, Norway
2
Institute of Clinical Medicine, University of Oslo, Oslo, Norway
3
Center for Heart Failure Research, University of Oslo, Oslo, Norway
4
Department of Medical Biochemistry, Oslo University Hospital, Ullevål, Norway
functions and how it is integrated with other regulatory
mechanisms. Certainly, more studies in the miRNA
field are definitive necessary to establish miRNAs as
reliable and useful biomarkers.
MicroRNA biogenesis
MicroRNAs (miRNAs) in their mature and active form
are only 18-24 nucleotides long, single-stranded and
subcellularly localized in the cytoplasma after a multi-
step biogenesis (Fig.1). In line with other RNAs, miR-
NAs are transcribed from specific gene coding regions
by RNA polymerase II as a longer primary transcript
before they are modified through 5´-capping and
3
´-polyadenylation (3). In contrast to what we appre-
hend as traditional post transcriptional proceedings,
the miRNA precursor is termed pri-miRNA, includes
hairpin structures and is partly double stranded. Pri-
miRNA is shortly cleaved by the nuclear Drosha and
Pasha enzyme complex (4), forming a double stranded
pre-miRNA of approximately 60-70 basepairs, which is
actively transported out to the cytoplasmatic compart-
ment by Ran-GTP and the Exportin-5 receptor (5).
Before the endpoint of a short, single stranded, mature
miRNA is reached, the endonuclease Dicer enzyme
removes the hairpin loop followed by an RNA strand
unwinding step (6).
miRNA activity
Mature, cytoplasmatic miRNAs are subsequently incor-
porated into an Argonaut-containing RNA-induced
silencing complex (RISC), which are able to search
for and pair with complementary sequences among
surrounding mRNAs (7). Interaction of miRNA and
