Biology Reference
In-Depth Information
1
The Biogenesis and Functions of
MicroRNAs
Much attention has been focused on RNA interference as mode of regulating gene
expression. Three small RNAs have been identified, namely small interfering RNAs
(siRNAs), microRNAs (miRNAs) and the repeat-associated small interfering RNA
(rasiRNAs). The PIWI protein-interacting RNAs (piRNAs) are a distinct class of small
RNAs differing greatly from miRNAs, but they are similar to rasiRNAs. RNA inter-
ference technology is being seriously considered for application in the clinical context.
MiRNAs are significant regulators of many biological phenomena, such as embry-
onic development and differentiation, regulation of the immune system and the
pathogenesis of human disease; a varied role been now established. Unlike miRNAs,
siRNAs are believed to regulate gene expression only in organisms which possess
RNA-dependent RNA polymerase. So in mammals the biological functions subserved
by siRNAs are still uncertain. But not unlike miRNAs, siRNAs have been found to be
able to target mRNAs (messenger RNAs) possessing partially complementary bind-
ing sites in the 3′ UTR (Doench et al., 2003). Recently Watanabe et al. (2008
)
showed
that endogenous siRNAs do participate in the regulation of gene expression.
MiRNAs may be expressed in a tissue-specific manner and have been implicated
in development, differentiation, miRNAs more so than siRNAs; they have been
linked with the regulation of the immune system; they participate in cell behaviour
related tumour development and progression. Some are regarded as tumour suppres-
sors, often down-regulated in tumour and therefore induced re-expression has been
viewed as potential approach to therapy. MiRNAs are also key players in differentia-
tion and pattern formation in early embryonic development. These systems together
with neoplasia are characterised by phenotypic cellular changes such as epithelial
mesenchymal transition (EMT) (see Sherbet, 2011a). These regulator RNAs influ-
ence the expression of oncogenes, suppressor genes, and growth and cell cycle reg-
ulator genes among others. These functions of the regulatory molecules have been
highlighted and intensively investigated in the past few years.
The miRNAs and siRNAs are approximately 21-26 nucleotides long and possess
similar function, but they differ in their modes of biogenesis (Carmell and Hannon,
2004; Kim, 2005). Importantly siRNAs are frequently derived from exons of genes
and so match the corresponding mRNAs precisely, whilst miRNAs are derived from
intronic sequences (Ambros et al., 2003; Lee et al., 2006; Duchaine et al., 2006;
Chapman and Carrington, 2007).
Genes that encode miRNAs are first transcribed into primary miRNA which can
form a stem-loop structure. These primary miRNA transcripts are processed by a
complex called the microprocessor complex formed of an RNase III Drosha (the
catalytic subunit) and the protein DGCR8 (DiGeorge syndrome critical region 8)
