Correspondence: Dirk Grimm firstname.lastname@example.org
Silence 2011, 2:8 doi:10.1186/1758-907X-2-8
(2011-11-30 10:38) University of Crete
Currently, I read the interesting minireview by Grimm in Silence journal (doi:10.1186/1758-907X-2-8),
concerning siRNAs�� toxic effects in cell vitality as it was probed in vivo. According
to this paper, it has been collectively reported in different works that the desirable
effect of RNAi bioassays is dependent on the small RNAs�� dosage. In other words,
there are some limitations in the efficiency of small RNAs�� action per se, due to
a `saturating�� plateau referring, not only to the RNA silencing mechanism sensitivity
but also in the consequences of those universal `entities�� on cellular homeostasis.
Far away from transgenic constructions, let��s give a glance at the role of endogenous
non-coding RNAs in a wild-type cell; it ranges from the `buffering�� the genome integrity
(Ha et al., 2009) to the synergistic interaction between nucleus and subcellular organelles
(e.g. mitochondrion), (Rackham et al., 2011). The diversity of those biological circumstances
imposes the need for other also aspects of this `RNA component�� to be integrated,
besides the mechanistic principles of RNA silencing itself.
In parallel with the contribution of Grimm and being inspired by various examples
of ecological extremity in time and space that sequentially affects small RNAs�� performance;
I would like to pose a hypothesis, as you can follow:
The dynamic micro-environmental conditions inside the intra-/inter-cellular space
make likely the RNA silencing machinery to behave as a dynamic `rheostat�� resulting
on oscillative small RNAs�� populations. Taking into account that the biophysical
and the structural features of bona fide siRNAs are evolutionary conserved among different
eukaryotes (Tang and Zamore, 2004), the small RNA pool maybe has to be considered
as a biochemical `ontogeny��, in a quantitative view. Such approaches could be followed,
independently of the (model) organism and the physiological condition studied. For
instance, the involvement of magnesium ions in RISC activity (reviewed by Kawamata
and Tomari, 2010) as well as the Michaelis-Menten turnover properties of the last
(Haley and Zamore, 2004; Brown et al., 2005) could be combined by a such logic.
Towards this aim, I am wondering if a functional correlation can be supported between
non-coding RNAs and the evolutionary formation of mRNP granules (P-bodies and stress
granules), (reviewed by Erickson and Lykke-Andersen, 2011) due to such phenomena mentioned
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