Cut & Run Gene Regulation

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. He previously identified a subset of messenger RNA molecules that are retained in the nucleus instead of being transported to the cyptoplasm for translation.  Further examination of one of these retained RNAs (CTN-RNA) led to the observation that under certain conditions (for example, stress), the RNA would be cleaved and immediately exported from the nucleus.  These observations suggest a novel gene regulation mechanism by which messages are held in reserve in the nucleus until there is an appropriate stimulus that sets off a process to cleave the RNAs and release them for transport to the cytoplasm where they can be expressed.  This allows an extremely rapid production of the protein product that does not depend on the time-consuming process of transcription to produce new messenger RNAs.  A deeper understanding of this rapid response, "cut and run" mechanism is predicted to have broad implications for biology and biomedical research.



Figure Legend

In unstressed cells (upper cell), two alternative mRNAs are produced.  The blue mRNA  (c) can move to the cytoplasm for translation while the red RNAs (a and b) are retained in the nucleus.
Upon stress (lower cell), the nuclear pool of red RNAs are posttranscriptionally cleaved in the 3′UTR (d). The released mRNA (f, red) is transported to the cytoplasm and translated into protein.
This mechanism provides a rapid response for the production of a protein that may be required under stress conditions.


Publication

Prasanth, K.V., Prasanth, S.G., Xuan, Z., Hearn, S., Freier, S.M., Bennett, C.F., Zhang, M.Q. and Spector, D.L.  2005.  Regulating gene expression through RNA nuclear retention.  Cell 123, 249-263. Abstract, Full Text