497a specific AGO isoform. AGO2 and perfect complementarity result in a direct
endonucleolytic cleavage; this effect requires only AGO2 loaded with a small
RNA. Other combinations result in translational repression followed by mRNA
destabilization and require fully formed effector complex containing translational
repressor GW182 (reviewed in Braun et al. 2013 ). The miRNA pathway is the
dominant small RNA pathway in animals—miRNAs are present in all cell types,
and there is an ever- growing list of essential roles of miRNAs in a broad variety
of cells and biological processes.
Next-generation sequencing of small RNAs during mouse OET revealed that
maternal miRNAs are a relatively minor small RNA population in oocytes (Ohnishi
et al. 2010 ; Garcia-Lopez et al. 2014 ). This notion is also consistent with the zebraf-
ish and Xenopus miRNA analyses (Chen et al. 2005 ; Tang and Maxwell 2008 ; Yao
et al. 2014 ); it appears that vertebrate oocytes do not accumulate maternal miRNAs
during the growth phase. An exception of the rule might be miR-202-5p, which was
reported to be enriched in Xenopus oocytes (Armisen et al. 2009 ). Although miR-
NAs can be detected in the sperm and may end up in the zygote, paternal miRNAs
are extremely unlikely to contribute to OET as their levels would be too low to have
significant effects (Amanai et al. 2006 ).
So far, there is no strong evidence for an important miRNA role in growing or
fully grown oocytes. Dicer-deficient zebrafish oocytes develop and can be success-
fully fertilized (Giraldez et al. 2005 ). The phenotype in maternal/zygotic Dicer
mutant fish appears during gastrulation and neural development and can be largely
rescued by zygotic miR-430 miRNA (Giraldez et al. 2005 ). This suggests that
maternal Dicer functions in biogenesis of zygotic miRNAs, while maternal miR-
NAs are functionally nonessential. A similar observation was made in the oocyte-
specific conditional mouse knockout of Dgcr8, an essential miRNA biogenesis
factor (Suh et al. 2010 ). Mouse oocytes lacking canonical miRNAs can be fertilized
and develop to the term. Maternal/zygotic Dgcr8 mutants can activate the genome
and develop until the blastocyst stage (Suh et al. 2010 ).
Interestingly, canonical maternal miRNAs become nonfunctional in the mouse
model in growing oocytes although their biogenesis and loading on AGO2 remain
apparently intact (Ma et al. 2010 ). Uncoupling miRNAs from the repression of
translation could be seen as the earliest known elimination of a parental factor dur-
ing OET in the mouse. According to the proposed model, the global suppression of
miRNA activity during OET facilitates the exchange of maternal and zygotic miR-
NAs in a gear-shift analogy: maternal miRNAs (e.g., Let-7 family) are disengaged
from translational repression and replaced by zygotic miRNAs (e.g., miR-290 clus-
ter), which become engaged when they reach significant amounts around the 8-cell/
morula stages (Svoboda 2010 ). The molecular mechanism responsible for suppres-
sion of miRNAs in mouse oocytes remains unknown.
At this point, the dynamics of vertebrate maternal miRNA clearance is not clear,
as high-throughput datasets from different vertebrate models do not completely
cover miRNA changes during meiotic maturation. One wave of maternal miRNA
degradation is induced by fertilization as reported for mice (Garcia-Lopez et al.
2014 ; Tang et al. 2007 ). This degradation appears global as all tested miRNAs
10 Clearance of Parental Products