Biology Reference
In-Depth Information
protein-based regulation showed that small RNA-based mechanisms are
better at filtering noise in input signals ( Mehta et al., 2008 ). Osella et al.
(2011) computationally analyzed the ability of FFLs containing miRNAs to
buffer noise, and they found that miRNAs can confer efficient noise control
in the face of fluctuations of the upstream nodes. Thus, miRNA FFLs are
predicted to buffer noise, as Ghosh et al. (2005) found for protein-only FFL
models. Interestingly, Osella et al. (2011) found that optimal noise filtering
does not necessarily require strong repression. Indeed, weak repression is a
common feature of most miRNA-target interactions. It is possible that the
networks that use miRNA-containing FFLs for buffering might have
selected miRNAs for modest repression. This could explain a frequent
paradox existing for many miRNAs, that is, an apparent dispensability and
lack of strong phenotypic consequences when individually knocked out but
a strong evolutionary conservation.
3. Conclusion
Robustness triggered by miRNAs is generally thought to be a conse-
quence of the way in which miRNAs act upon their gene targets. While
this principle is no doubt at work, we have attempted to discuss miRNAs in
the context of simple and complex networks of regulation. miRNAs
regulate circuits that can provide robustness to networks. Within networks,
miRNAs favor regulation of central hubs and bottlenecks. Their regulation
is frequently module-centric, and targeting propensity increases toward the
downstream effectors of signaling networks. These biases in miRNA target-
ing are, in and of themselves, other means by which miRNAs more
effectively generate robustness. These biases would then imply that the
acquisition of targets by miRNAs is not necessarily to generate novel gene
regulation but to stabilize gene networks. This idea would explain why
experimentalists frequently observe few phenotypic changes when highly
conserved miRNAs are mutated. It also begs the question as to whether the
extraordinary high birth and death rates of animal miRNA genes ( Lu et al .,
2008 ) might reflect dynamic buffering of gene expression prior to and
subsequent to speciation.
ACKNOWLEDGMENTS
We thank Justin Cassidy, Adam Pah, and Patrick McMullen for helpful discussions. This
work was funded by the NIH (GM077581), the Chicago Center for Systems Biology
(CCSB), the Chicago Biomedical Consortium (CBC) with support from The Searle
Funds at The Chicago Community Trust, and the Malkin Scholars Program from the
Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
Search WWH ::




Custom Search