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FMI

March 20, 2012

Inhibiting RNA in the nucleus to stay tuned for an emergency response

Scientists from the Friedrich Miescher Institute for Biomedical Research discovered a new RNA interference mechanism that controls transcripts in the nucleus as they are produced. They could show that this is particularly important for a cell to be prepared for emergency situations where a rapid, immediate response is of essence. The results have been published today online in the renowned journal Genes & Development.

When faced with danger the body prepares immediately for the emergency. In humans this ranges from adrenalin and endorphin secretion to sharpening of the senses, increased heart rates and acceleration of the metabolism for emergency actions. But these processes are not limited to mammals. Even organisms as simple as yeast maintain emergency mechanisms that help them survive harmful situations. For yeast, a temperature increase of 9°C is life-threatening. In this situation, a group of so called "heat-shock proteins" takes over control and prepares the cell for survival.

RNA biologists from the Friedrich Miescher Institute for Biomedical Research have now discovered a novel mechanism that is involved in the regulation of rapid emergency responses in the fission yeast Schizosaccharomyces pombe. As Katrina Woolcock and her colleagues publish today online in Genes & Development, they could show that RNA interference (RNAi), the process during which small interfering RNA pieces target RNA transcripts for destruction, plays an important role. They show that transcription of stress-response genes is not completely blocked under non-stressful conditions. However, the RNAi machinery at nuclear pores, the gateway from the cell's nucleus to the cytoplasm, tightly represses expression of these genes. Thus, interfering RNA fragments ensure that transcripts produced from stress-response genes are being degraded and do not wrongfully flash into action. In an emergency, for example when temperatures rise, the increased production of heat-shock protein RNA overpowers the effects of RNAi. If the heat persists, Dicer, one of the key proteins in the RNAi pathway, changes its form and moves out of the nucleus, thereby allowing the adaptations in the cell that help them to survive at higher temperatures.

"These results are exciting for two reasons", comments Woolcock's supervisor Marc Bühler, group leader at the FMI, "so far we thought that interfering RNA species play an ancillary role in the nucleus. RNA interference was known to happen predominantly in the cytoplasm. In the nucleus, we did know that they control the formation of the denser regions of the genome called heterochromatin in some organisms, but we did not think it interfered in any other way with the expression of genetic information. And it is for the first time that anybody could show that RNAi functions in the nucleus to directly control protein-coding genes. That newly synthesized RNA is being controlled by RNAi in association with chromatin and nuclear pores constitutes a novel concept of gene regulation." It remains to be seen whether this process is also employed in other organisms or for other processes that need a fast and immediate reaction.

On Katrina Woolcock and Marc Bühler
Katrina Woolcock is a PhD student in the research group of Marc Bühler. Marc Bühler's research interest focuses on the role of non-coding RNAs and processing thereof in the regulation of genetic information.
» More about Marc Bühler

Original publication
Woolcock KJ, Stunnenberg R, Gaidatzis D, Hotz H-R, Emmerth S, Barraud P, Bühler M (2012) RNA interference keeps Atf1-bound stress response genes in check at nuclear pores. Gen & Dev, Advanced online publication, March 19, 2012, doi: 10.1101/gad.186866.112

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