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Carnegie Mellon University research reveals how cells process large genes

Important messages require accurate transmission. Big genes are especially challenging because they combine many coding segments (exons) that lie between long stretches of non-coding elements (introns). During processing, introns are snipped out and exons pasted together to form a template for proteins called messenger RNA (mRNA). Mistakes in RNA processing can reduce the expression of a functional protein or, worse, produce an abnormal protein that interferes with normal cell behavior. But just how a cell's molecular machinery eliminates long introns without making errors has puzzled scientists for years.

Now, investigators at Carnegie Mellon University have discovered that a novel mechanism, called recursive splicing, removes long introns by steadily paring them down in a predictable fashion and joining the remaining exons. The findings are published this summer in Genetics. This process, which the investigators discovered in the fruit fly Drosophila, has been conserved over tens of millions of years of insect evolution and also appears likely to occur in humans, according to the investigators.

"While some scientists have suspected that large introns might not be removed in one piece through direct splicing, no one had identified how this could happen. Now we have identified a way," said Antonio-Javier Lopez, professor of biological sciences at Carnegie Mellon. Ultimately, recursive splicing could be responsible for thwarting molecular mishaps in the expression of large human genes associated with diseases like muscular dystrophy, cystic fibrosis and cancer.

"We found that many large introns are removed by multiple recursive splicing steps," Lopez said. "These steps involve the sequential excision of smaller subfragments. Our work also indicates that most recursive splicing events leave no clues in the final mRNA. This is why they have not been detected before now."

These previously undetected events could have profound implicati
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Source:Carnegie Mellon University


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