Cell Biology
David Spector and his colleagues have discovered a new molecular mechanism
that is likely to control the production of many proteins in humans and other
organisms. A deeper understanding of this rapid response, "cut and run" mechanism
is predicted to have broad implications for biology and biomedical research.
A few years ago, members of David's group noticed that under standard growth
conditions, a particular subset of messenger RNA molecules lingered in the
nucleus indefinitely (in structures called "speckles") and never
reached the cytoplasm as they typically do.
Spearheaded by the work of Kannanganattu Prasanth, David's group discovered
a new paradigm of gene regulation that explains why such atypical messenger
RNAs linger in the nucleus instead of being used immediately to produce protein.
First, they found that a mouse gene called mCAT2 encodes two different kinds
of messenger RNA: a standard protein coding version that's exported to the
cytoplasm soon after it is produced in the nucleus, and an atypical version
that lingers in the nucleus.
Those observations led David and his colleagues to propose that when cells
are stressed (e.g. by viral infection), perhaps the lingering mCAT2 messenger
RNAs are rapidly released from the nucleus and exported to the cytoplasm, thus
circumventing the time-consuming process of producing new messenger RNA needed
for stress response.
Confirming this idea, they discovered that the atypical mCAT2 messenger RNAs
in the nucleus were rapidly cleaved in response to interferon treatment (which
mimics the effect of viral infection), and that the protein-coding portion
of the messenger RNAs was indeed then rapidly exported to the cytoplasm and
translated into protein. David has reason to believe that many genes in humans
and other organisms that need to be rapidly induced are regulated in this way.
Because the protein coding regions of most mammalian genes are interrupted
by large segments of DNA (called introns), a phenomenon discovered at Cold
Spring Harbor Laboratory in 1997, leading to a Nobel Prize, it can take many
hours to copy the DNA into mRNA. The new mechanism of gene regulation discovered
by David and his colleagues may explain how genes can be rapidly expressed
when cells receive an appropriate signal. |
