We
just learned something very important in terms of the management of
gene expression. Importantly, it is an ongoing process that can also
be plausibly managed by the organism to achieve results.
One
wonders what else we may be missing and what the biochemical flow
chart actually looks like today
What
has always intrigued me in reviewing work around the operations of
genetics has been the natural robustness and the actual lack of a
absolutely clear idea of OFF and ON. What we get instead is an OFF
bell curve and an ON bell curve. On top of all that it is not
exclusively a binary process. Yet it is still a logic engine.
This
may actually be the missing link in our understanding of the whole
pattern. Something had to be changing in this way.
RNA breakthrough
transforms idea of gene control
18 May 2012 by Andy
Coghlan
Tiny chemical
changes that do not alter the sequence of our DNA but modulate how it
works have been found to act on a new part of our genetic machinery.
The discovery could provide insights into many health problems,
including obesity.
It has been long known
that DNA can be altered "epigenetically" – where changes
occur without altering the sequence of DNA but leave chemical marks
on genes that dictate how active they are by adding chemical methyl
groups that silence genes, for example. Numerous environmental
factors, such as stress and smoking, have been shown to influence
these epigenetic marks.
Now, researchers have
discovered that messenger RNA, the mirror-image copy of DNA from
which all proteins are manufactured, can be methylated too.
"We've
discovered something fundamental to biology," says Samie Jaffrey
of Cornell University in New York, and head of the team that made the
discovery. "It was there all the time and no-one knew about it."
Fundamental discovery
Jaffrey's team found
that around a fifth of the RNA produced in cells from rat brains and
human kidneys contained methylated versions of adenosine, one of the
four building blocks of our genetic code. "It was exciting to
find that 20 per cent had methyl groups, so it must be a pretty
fundamental regulatory mechanism," says Jaffrey.
Separate analyses of
assorted rat tissues demonstrated that the methylated RNA was
concentrated in the brain, liver and kidneys. Also, samples from rat
embryos showed that concentrations rose 70-fold in the brain as it
reached the final stages of growth, therefore they are likely to play
a fundamental role in development.
The team also
discovered that the methyl groups are stripped off the RNA by an
enzyme linked with obesity. The enzyme is made by a gene called
FTO, one variant of which raises the risk of obesity by 70 per cent.
People with an overactive copy of the gene are most at risk,
suggesting that stripping the methyl groups from RNA might somehow
alter our metabolism.
The researchers found
that methylated adenosine tended to cluster close to the point on the
RNA strand where protein manufacture reaches completion, and on
regions where other proteins bind to the strand to alter or halt
production. The suggestion is that methylation may therefore dictate
how much protein gets made, and when. "It's not changing what
would be made, but it might govern how much and when it's made,"
says Jaffrey. This, he says, could in turn have a big impact on a
multitude of physiological processes and disease.
Journal reference:
Cell, DOI: 10.1016/j.cell.2012.05.003t/k
