Quiescent cells brings to light the essential role of RNA interference


Think about the genetic material or
the DNA of a chromosome all cells have to make a fundamental
decision as to whether transcribe that DNA into RNA which will then allow the
function of the cell production proteins and so on or to replicate it into more
DNA and these two are competing functions between the RNA polymerase and
the DNA polymerase responsible for replication we work on something called
RNA interference which we showed about 15 years ago now can silence genes by
removing RNA polymerase 2 and by stimulating the production of something
called heterochromatin the most condensed part of the chromosome which
doesn’t allow transcription and it promotes our RNAi promotes the
formation of heterochromatin which has important functions in chromosome
segregation we work with the model organism called fission yeast they’re
very simple and they have RNA interference but when we make mutants in
these fission yeast that no longer have the RNA interference they can no longer
silence genes using by removing RNA polymerase 2 but what we found is that
they can no longer survive without DNA replication in a quiescent state now
most cells in animals and plants are non-dividing that doesn’t mean they’re
not alive they can be stimulated quiescent cells can be stimulated to
re-enter the cell cycle and because this involves both the reprogramming from
division to quiescence and the stable maintenance of quiescence for very long
periods but in a reversible way we can think of this as an epigenetic
transition so they’re not changing their genetic constitution while doing this
but they must be doing something that’s both reversible on the one hand and very
stable on the other in order to be able to maintain and enter this this
quiescent state and so RNA interference is one of the most important epigenetic
mechanisms it guides many of the other epigenetic mechanisms and so perhaps it
should come as no surprise that you need RNA interference to enter and maintain
quiescence we found through genetic analysis that the reason for this was
the RNA interference seems to interact
genetically with transcription itself with the RNA polymerase both RNA
polymerase one which is responsible for our DNA ribosomal DNA transcription as
well as RNA polymerase 2 which transcribes the rest of the genome and
by releasing these at different points in the cell cycle either in dividing
cells or quiescence RNAi controls the formation of the silent compact
heterochromatic domains if those domains get are unmanaged if they get out of
control they will kill the cell and that’s what’s happening in quiescent
cells that don’t have RNAi one of the things that this explains very neatly is
that organisms that have lost RNAi naturally in nature and there are a few
of these have also lost heterochromatin they have to because otherwise the
toxic heterochromatin would kill them during quiescence so this is a very very
powerful explanation for this interesting evolutionary trend
importantly it might also explain the key role that RNAi plays in stem cells
which are quiescent for much of their life and also in cancer which after all
is the stimulation of cells that are normally quiescent normal benign cells
of the body to divide and proliferate and that transition is often accompanied
by mutations in RNAi just like our mutations in fission yeast. you

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