Scientists discover role for dueling
RNAs
CAMBRIDGE, Mass. (Nov. 16, 2006) — Researchers
have found that a class of RNA molecules, previously
thought to have no function, may in fact protect sex
cells from self-destructing. These findings will be
published in the November 17 issue of the journal Cell.
Central to this discovery is the fundamental process
of gene expression. When a gene is ready to produce
a protein, the two strands of DNA that comprise the
gene unravel. The first strand produces a molecule called
messenger RNA, which acts as the protein’s template.
Biologists call this first strand of DNA the “sense”
or “coding” transcript. Even though the
other strand doesn’t contain a protein recipe,
it may also, on occasion, produce an “anti-sense”
RNA molecule, one whose sequence is complementary to
that of the messenger, or sense, RNA. Antisense RNA
has been detected for a number of genes, but is largely
considered a genetic oddity.
“This is the first case where a specific
function in a higher cell for antisense RNA has
been found,” says Whitehead Member Gerald
Fink. “This points to an entirely new process
of gene regulation that we’ve never seen
before in eukaryotic cells.” |
Using common baker’s yeast, Cintia Hongay, a
postdoctoral researcher in the lab of Whitehead Member
and MIT Professor Gerald
Fink, discovered that in the case of a gene called
IME4, the antisense RNA blocks the sense RNA.
In other words, the gene disables its own ability to
make protein.
“This is the first case where a specific function
in a higher cell for antisense RNA has been found,”
says Fink, senior author on the paper. “This points
to an entirely new process of gene regulation that we’ve
never seen before in eukaryotic cells.”
There is a method to this sense/antisense madness,
one that has a kind of yin and yang quality. When conditions
around yeast cells are good and rich in nutrients, the
cells divide by mitosis—that is, the DNA duplicates
so each daughter cell receives exactly the same number
of chromosomes as the original cell. However, when the
yeast cells are starving, IME4 switches on
and activates a process called meiosis. Here, the cells
divide into germ-cell spores that, like mammalian egg
and sperm cells, have half the number of chromosomes.
Yeast spores withstand this harsh environment far more
ably than the larger cells from which they originate.
But in some cases, flipping the meiotic switch can
be catastrophic. If a cell with only one copy of each
chromosome (a haploid cell) is forced into meiosis,
the progeny won’t survive. Fortunately, such destructive
meiotic division is avoided in haploid cells because
they continually produce IME4 antisense RNA,
blocking the production of sense RNA. Antisense IME4,
then, safeguards against meiosis in cells that can’t
handle it.
“This is the first time that we’ve found
a function for antisense RNA, that is not RNAi, in a
higher cell type,” says Hongay. “In fact,
it’s really the first time we’ve seen a
gene regulate itself in this way.”
“For years scientists have evaluated genomes by
measuring the sense RNA, with antisense transcripts
thought to have no meaning at all,” says Fink.
“Here we’ve found a process in which antisense
RNA regulates sense RNA. This same process may occur
in the sex cells of mammals. In fact, considering how
widespread these antisense transcripts are, I wouldn’t
be surprised if these findings eventually lead us to
discover an entirely new level of gene regulation.”
Hongay is now searching the yeast genome for other genes
that might be regulated by antisense RNA.
This work was supported by the National Institutes of
Health. Cintia Hongay is supported by a Ruth L. Kirschstein
NRSA postodoctoral fellowship.
|
