Case Western Reserve finds mechanism underlying alt. splicing of premessenger RNA into mes...( CLEVELAND December 24 2008 An inte...)

CLEVELAND December 24, 2008 An international research team led by Tim Nilsen, Ph.D., a professor of medicine and biochemistry and the director of the School of Medicine's Center for RNA Molecular Biology, has discovered an unexpected mechanism governing alternative splicing, the process by which single genes produce different proteins in different situations. The new mechanism suggests that curing the more than half of genetic diseases that are caused by mutations in the genetic code that in turn create mistakes in alternative splicing may be considerably more complicated than biomedical researchers have previously assumed. Those diseases include a large number of cancers and many neurodegenerative diseases.

The research, titled "Dynamic regulation of alternative splicing by silencers that modulate 5' splice site competition" is published in the December 24 issue of Cell. Nilsen led an international team of researchers from Case Western Reserve University, Columbia University, Memorial Sloan-Kettering Cancer Institute in New York City, and the Max Planck Institute for Biophysical Chemistry in, Germany. Case post-doctoral fellow Yang Yu, Ph.D. was the lead author.

"Regular" splicing is the process by which long strings of nucleotides in a gene's pre-messenger RNA (pre-mRNA) are discarded, and the remaining strings of nucleotides are spliced together into one continuous strand of messenger RNA (mRNA) that produces one unique protein.

But regular splicing is insufficient to produce all the proteins in the human cell, where 25,000 genes surprisingly produce more than 100,000 proteins. The additional 75,000 proteins are created by alternative splicing, a process that selectively activates alternate splicing sites along the pre-messenger RNA strand to assemble different subsets of RNA nucleotides into a variety of mRNA's. Each mRNA then produces a single protein. The vast majority of genes utilize alternative splicing.

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