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| 2 | 2011
Klinisk Biokemi i Norden
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Fortsætter side 36)
complementary binding sites on target mRNAs mainly
facilitates downregulation of the protein synthesis by
post transcriptional inhibition through either trans-
lational repression or degradation of mRNA through
destabilization. The mechanism for target regulation
is yet not fully clarified, but the mode of repression
may depend on the level of complementarity between
miRNA and mRNA target. Perfect or close to perfect
base-pairing favour mRNA degradation, whereas lower
grade sequence homology promotes translational inhi-
bition (8,9). On the contrary, recent evidence suggests
that miRNAmay also upregulate translation of selected
targets (9).
The 5´-region of a miRNA, designated the “seed
region” (nucleotide number 2-8), has shown to be cru-
cial for binding the right mRNA, and is therefore of
major importance for miRNA targeting and function
(10).
Binding is most often imperfect and principally
located in the 3´-untranslated region (UTR) of target
mRNAs, but has also been found to be situated in the
5
´ UTR or in coding regions (11). Because functional
miRNA activity does not require perfect sequence
homology between the miRNA and the target mRNA
strands, a single miRNA can regulate several different
mRNA targets. Moreover, the flexibility of the base-
pairing allow multiple miRNAs to regulate one mRNA
(
Fig. 2). In this way, miRNAs have theoretically the
capacity to control the expression of a broad range of
different target proteins, which again can affect a myriad
of down stream cell regulatory pathways.
The functional range of the miRNAs is exerted
through their regulation of specific sets of target bind-
ing. So far, target prediction has been a difficult task,
but the recent development of sequence-matching
algorithms, which identify putative miRNA targets, may
improve model accuracy. The mechanism of miRNAs
and their contribution to regulation of gene expres-
sion through sequence-specific basepairing with target
mRNAs are not fully understood, but it is estimated that
up to 50 % of the 30 000 human genes may be potential
targets for the miRNAs (12).
Figure 1. The multistep biogenesis of mature miRNA.
