The Role of MicroRNAs in Natural Tissue Development and Application in Regenerative Medicine - RNA Interference from Biology to Therapeutics - page 59

Fig. 3.2 Overview of RNAi cellular pathways with focus on miRNA processing. In the nucleus,
pri-miRNA are transcribed and subsequently processed by Drosha into hairpin-structured pre-
miRNA. These are exported to the cytoplasm where they are trimmed into double-stranded RNAs
of ~19-21 base pairs by Dicer. One of the strands is incorporated into the RISC complex as the
mature miRNA. The 5¢ 2-8 nucleotides of the mature miRNA constitute the seed sequence which
guides the RISC complex to mRNAs by complementary base pairing. The translation of these
mRNAs is then abrogated, and the mRNAs are usually destabilised, leading to a decline in protein
expression
are called small interfering RNAs (siRNA) or miRNA mimics. Proteins, including
the argonaute protein, are recruited to form the precursor RNA-induced silencing
complex (pre-RISC). The strand with less stable base pairing at the 5¢ -end, called
the guide strand, remains in the RISC complex as the mature miRNA while the pas-
senger strand is degraded.
This miRNA guides the RISC to the mRNA, usually to a site within the 3¢
untranslated region. The specificity is mainly directed by a perfect match to the so-
called seed sequence, which spans position 2-8 in the miRNA. This leads to trans-
lational repression and usually also increased mRNA degradation. The remaining
part of the sequence can modulate the effect, and more extensive matches can lead
to Ago-2-mediated cleavage of the target, which is often the case with artificially
constructed siRNA [ 16 ] .
Endogenous miRNA levels can be transiently upregulated by delivering exoge-
nous pre-miRNAs [ 17 ] or pri-miRNAs [ 18 ]; alternatively, the function of a miRNA