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Noncoding RNA may promote Alzheimer's disease

31.05.2011
Researchers pinpoint a small RNA that spurs cells to manufacture a particular splice variant of a key neuronal protein, potentially promoting Alzheimer's disease (AD) or other types of neurodegeneration. The study appears in the May 30 issue of The Journal of Cell Biology (www.jcb.org).

Like a movie with an alternate ending, a protein can come in more than one version. Although scientists have identified numerous proteins and RNAs that influence alternative splicing, they haven't deciphered how cells fine-tune the process to produce specific protein versions. Four years ago, researchers identified a set of 30 small, noncoding RNAs that they suspected help regulate gene expression.

Italian researchers have now determined the function of one of the RNA snippets, known as 38A, that hails from a noncoding part of the gene that encodes the protein KCNIP4. KCNIP4 helps ensure that neurons fire impulses in a characteristic slow, repeating pattern. The researchers found that 38A spurs cells to produce an alternative splice variant of KCNIP4, Var IV, that disrupts this current, potentially leading to neurodegeneration.

KCNIP4 normally interacts with gamma-secretase, the enzyme complex that helps generate beta-amyloid (Abeta), a protein that accumulates in the brains of AD patients. But Var IV can't make the connection, possibly disturbing Abeta processing. Supporting that notion, the researchers found that levels of 38A were more than 10 times higher in brain cells from AD patients than in controls and that 38A hiked output of the more dangerous Abeta isoform Abeta 1-42.

About The Journal of Cell Biology

Founded in 1955, The Journal of Cell Biology (JCB) is published by The Rockefeller University Press. All editorial deci-sions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JCB content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit www.jcb.org.

Massone, S., et al. 2011. J. Cell Biol. doi:10.1083/jcb.201011053.

Rita Sullivan | EurekAlert!
Further information:
http://www.jcb.org
http://www.rupress.org

Further reports about: Abeta JCB KCNIP4 RNA brain cell cell death noncoding synthetic biology

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