Biology Reference
In-Depth Information
A Suppression of miRNA loss-of-function phenotype
Wild-type
Mutant
Epistasis
miRNA
miRNA
miRNA
Heterozygosity
of target
Target(s)
Target(s)
Target(s)
Expression of
RNAi transgene
Phenotype caused by
overactive target(s)
Phenotype
suppressed
B Enhancement of miRNA gain-of-function phenotype
Wild-type
Ectopic miRNA
Epistasis
miRNA
miRNA
miRNA
Heterozygosity
of target
Target(s)
Target(s)
Target(s)
Expression of
RNAi transgene
Phenotype caused by
underactive target(s)
Phenotype
enhanced
Figure 8.3
Usage of genetic interactions to elucidate miRNA function. Since miRNAs
act by repressing target genes, the phenotypic outcome of modulatingmiRNA activity can
be sensitive to the dose of the key miRNA target(s). (A) In a miRNA loss-of-function
condition, crucial target(s) are derepressed, leading to a phenotype. Lowering the dose of
these target(s) by heterozygosity or RNAi can reduce the target levels to below a pheno-
typic threshold and suppress the phenotype. This situation can only be fulfilledwhen there
are individual target genes that contribute substantially to organismal phenotype; never-
theless, this seems to be common among Drosophila miRNA mutants. (B) In a miRNA
gain-of-function condition, a phenotype can arise due to crucial target(s) being lowered to
levels below a phenotypic threshold. Heterozygosity or RNAi knockdown of these target
(s) can enhance this phenotype. Note that for both loss- and gain-of-function miRNA
conditions, the observation of genetic interactions with target heterozygosity is more
powerful than the usage of RNAi transgenes. Target knockdown often generates pheno-
types on its own, whereas heterozygosity is usually phenotypically benign.
factors typically bind thousands of genomic regions (
Gerstein
et al
., 2010
;
Macquarrie
et al
., 2011
;
Roy
et al
., 2010
), and that these are often conserved
(
Birney
et al
., 2007
;
He
et al
., 2011
;
Stark
et al
., 2007
). Nevertheless, it is
