Members of the ribonuclease III superfamily of
double-stranded (ds)
RNA-specific
endoribonucleases participate in diverse
RNA maturation and decay pathways in
eukaryotic and
prokaryotic cells. The
RNase III Drosha is the core
nuclease that executes the initiation step of
microRNA (miRNA) processing in the
nucleus. The microRNAs thus generated are short
RNA molecules that regulate a wide variety of other genes by interacting with the
RNA-induced silencing complex (RISC) to induce cleavage of
complementary messenger RNA (mRNA) as part of the
RNA interference pathway. MicroRNA molecules are synthesized as long RNA
primary transcripts known as a
pri-miRNAs, which are cleaved by Drosha to produce a characteristic
stem-loop structure of about 70
base pairs long, known as a
pre-miRNA. Drosha exists as part of a
protein complex called the
Microprocessor complex, which also contains the double-stranded RNA binding protein
DGCR8 (called
Pasha in
D. melanogaster and
C. elegans). DGCR8 is essential for Drosha activity and is capable of binding single-stranded fragments of the pri-miRNA that are required for proper processing. The Drosha complex also contains several auxiliary factors such as
EWSR1, FUS,
hnRNPs, p68, and p72. This variant has been shown to localize to the cell
cytoplasm rather than the nucleus, but the effects on pri-miRNA processing are yet unclear. Both Drosha and Dicer also participate in the
DNA damage response. Certain miRNAs have been found to deviate from conventional biogenesis pathways and do not necessarily require Drosha or
Dicer, which is because they do not require the processing of pri-miRNA to pre-miRNA. Drosha-independent miRNAs derive from
mirtrons, which are genes that encode for miRNAs in their introns and make use of splicing to bypass Drosha cleavage. Simtrons are mirtron-like, splicing-independent, and do require Drosha mediated cleavage, although they do not require most proteins in the canonical pathway such as
DGCR8 or
Dicer. == Clinical significance ==