Biology Reference
In-Depth Information
(
He and Hannon 2004
). When double-stranded (ds) RNA is injected into eukary-
otic cells by transposable elements (or viruses), the ds RNA seems to function as a
signal that the cell is being invaded because most RNA in a cell is single-stranded.
Thus, ds RNA elicits a defense response—RNAi (
Matzke et al. 2001
). RNAi initially
was discovered in the nematode
Caenorhabditis elegans
, where it was found to
modify larval development (
Fire et al. 1998
). The discovery of RNAi resulted in a
Nobel Prize for Andrew Fire and Craig Mello in 2006. This discovery allows sci-
entists to determine the function of many previously unknown genes through
their silencing (
Mito et al. 2011
). RNAi is being developed as a method for ana-
lyzing gene functions in multiple species and orders of insects. RNAi also is being
investigated as a tool for modifying the development of pest insects (
Mito et al.
2011
). RNAi involves the use of miRNAs that degrade specific RNAs (
Figure 2.8
).
The sequencing of multiple genomes has allowed scientists to confirm that
miRNAs are evolutionarily conserved and are found in molluscs, sea urchins,
flies, mice, and humans. Such an evolutionary conservatism in gene sequence
indicates that these small RNAs are important in regulating the development
of many eukaryotic organisms (
Cernilogar et al. 2011
). miRNAs are 21-25nt
and are derived from longer ds RNAs that form imperfect stem-loop structures.
The miRNA is usually formed from one arm of the hairpin and is released after
two enzymatic processes involving the RNase III enzymes Drosha and Dicer fol-
lowed by subsequent processing in a protein complex (RISC) that includes the
Argonaute protein. Argonaute cleaves and discards the sense strand of the ds
RNA. The antisense strand of the RNA and the RISC protein complex then cleave
the homologous messenger RNA, resulting in a
loss of a specific gene function
.
The two-step reaction is efficient because each molecule of ds RNA primes sev-
eral RNase molecules, so the cell can mount a large-scale response to only a few
ds RNA molecules (
Baulcombe 2001
).
Cernilogar et al. (2011)
noted that RNAi
pathways not only modulate gene expression by degrading RNA target mol-
ecules in the cytoplasm but also have a function in the nucleus of
D. melano-
gaster
. They demonstrated that key RNAi components (Dicer and Argonaute)
associate with euchromatin, especially transcriptionally active loci, and interact
with the core transcription machinery. These RNAi components apparently con-
trol the processivity of RNA polymerase II in the nucleus.
After the genome of the silkworm,
Bombyx mori
, was sequenced,
Zhang
et al. (2009)
identified 354 miRNA genes and found that they were important
in embryogenesis and metamorphosis. Furthermore, the sequences of these
miRNAs were sufficiently different from those found in mammals and the nema-
tode
C. elegans
, to suggest that there are many miRNAs unique to insects.
Skalsky
et al. (2010)
evaluated miRNAs in the mosquitoes
Aedes albopictus
and
Culex
