Biology Reference
In-Depth Information
Chapter 2
MicroRNA Maturation and Human Disease
Marlen Hesse and Christoph Arenz
Abstract
Numerous studies describe alterations in the levels of specifi c microRNAs (miRNAs) that are associated
with human pathologies. Some of these alterations may give rise to the development of novel diagnostic
tools, while certain miRNAs additionally could serve as novel drug targets. Moreover, components of the
miRNA maturation machinery may be up- or down-regulated in human disease. In such cases, the conse-
quences for the expression of individual miRNAs are however only poorly understood. Herein, we review
the current knowledge of how miRNAs are linked to human disease and which parts of the miRNA
maturation machinery could serve as future drug targets.
Key words
miRNAs, Dicer, Drosha, Biomarkers, Drug targets
1
miRNA Function and Biogenesis
MicroRNAs (miRNAs) are small, noncoding, 21-25 nt regulatory
RNA molecules involved in physiological and pathological pro-
cesses [
1
,
2
]. First footsteps in discovering miRNA function and its
relevancy in gene regulation were set by identifying miRNA family
lin
-
4
lin-14
Caenorhabditis elegans
[
3
]. Lin-4 is indispensable for the
normal temporal control of postembryonic developmental events
lin-14
C
.
elegans
organism. Lee et al. found that lin-4 does not only
not
encode a protein, but, more importantly, it regulates lin-14 trans-
lation through “RNA-RNA interaction”. By negatively regulating
lin-14 protein levels, lin-4 enables a temporal decrease of that
protein during the fi rst larval stage (L1). This interaction was con-
fi rmed by identifying two small lin-4 transcripts of about 20 and
60 nt containing sequences complementary to a 3
-untranslated
sequence in lin-14 mRNA. Lin-14 protein is down-regulated dur-
ing late L1 and introduces switching to second larval stage (L2).
In fact, mutations in lin-14 let to unusual high amounts of lin-14
protein in nucleus from the beginning of L2 up to adult stages [
4
].
Analysis of those mutations clarifi ed that they are lesions in the
3
′
′
-untranslated region (UTR) of lin-14 [
5
]. As no protein-coding
