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Living view in animals shows how cells decide to make proteins

oduces within the cell.

The scissors that do the genetic chopping are, in most cells, proteins called splicing silencers and splicing enhancers.

In the current study, Garcia-Blanco’s team sought to identify which silencers chop out an important segment of RNA in a gene called fibroblast growth receptor 2 (FGFR2). This gene plays a critical role in normal mouse and human development, and the order in which its RNA is assembled can alter an animal’s development.

As a model system to study, the scientists genetically created a "glowing" mouse. The mouse carried in its FGFR2 gene a green fluorescent tag that would glow when a common type of silencer, called an "intronic silencer," chopped out a specific exon, called IIIb.

In this way, the scientists could track whether intronic silencers were chopping out the IIIb exon -- and if so, in which tissues and organs -- or whether other types of silencers or helper proteins were involved.

By tracking the green glow, the team found that cells in most tissues made the same decision to silence exon IIIb, but the cells used a variety of silencers and helper proteins to accomplish this task, said Vivian I. Bonano, a graduate student in the University Program in Genetics and Genomics and lead author of the journal report.

"Identifying which silencers are active in a given tissue or organ will ultimately help scientists understand how exons are erroneously included or excluded in various disease processes," Bonano said.

For example, a cell’s decision to include exon IIIb is critical because the exon’s presence or absence determines which variant of the FGFR2 protein is produced, she said. Such subtle variations in proteins can alter the cell’s behavior, just as switching ingredients in a favorite recipe can change the food’s flavor, according to the scientists.

"Viewing these decisions is most relevant in a living animal, because cells behave different
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Source:Duke University Medical Center


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