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Drosha-DiGeorge syndrome critical region gene 8 (Dgcr8) microprocessor
complex in the nucleus ( Denli et al ., 2004; Gregory et al ., 2004;Han et al ., 2004;
Landthaler et al ., 2004 ). However, in a few exceptions where the hairpin is
generated directly from transcription of short-hairpin RNA or derived from
splicing of a certain type of intron that is capable of folding into the hairpin
structure (also known as the mirtron pathway), the biogenesis of these
Steoreotypical
miRNAs
Mirtron
shRNA
pri-miRNA
Exon
Exon
G
AAAAA
G
AAAAA
Dgcr8
Spliceosome
Drosha
pre-miRNA
Splicing
(mirTron)
Xpo5
pre-miRNA
Nucleus
Dicing
Dicer
Cytoplasm
RISC
Dicer
Ago1−4
Translational inhibition
Deadenylation
mRNA cleavage
Ago2
Ago1−4
G
AAAAA
G
AAAAA
Figure 7.1 Dgcr8 and Dicer are essential components for miRNA biogenesis. Most
highly expressed miRs are transcribed as long RNA transcripts and processed by the
Drosha/Dgcr8 complex to liberate the hairpin precursor (pre-miRNA) in the nucleus.
However, a few miRs are either directly transcribed as short-hairpin (sh) RNA or pro-
cessed via splicing (themirtronpathway). Thus thesemiRs are independent of theDrosha/
Dgcr8 processing for the generation of the hairpin. After transported to the cytoplasm by
Xpo5, pre-miRNAs are further processed by Dicer. One strand of the double-stranded
RNA duplex is complexed with Ago proteins to form the RISC.
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