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RNA map provides first comprehensive understanding of alternative splicing

It's biology's version of the director's cut. In much the same way that numerous films could be stitched together from a single reel of raw footage, a molecular process called alternative splicing enables a single gene to produce multiple proteins. Now a new RNA map, created by a team of researchers at Rockefeller University and the Howard Hughes Medical Institute and announced in the journal Nature, shows for the first time how the specific location of short snippets of RNA affects the way that alternative splicing is controlled in the brain.

Though scientists have begun to appreciate how alternative splicing adds a layer of complexity to brain processes that enable us to think and learn, exactly how alternative splicing is regulated during these processes -- and in some cases is uncontrolled (or dysregulated) to cause disease -- has remained elusive. The map provides the first comprehensive understanding of how alternative splicing works throughout the genome. The results have implications for a better understanding of such brain functions as learning and memory, neurological diseases and cancer biology.

"This finding is a significant advance in our understanding of splicing, and it suggests that it will be possible to understand how different splicing factors weave together to regulate complex patterns of genes, which in turn is relevant to generating complexity of function," says senior author Robert Darnell, professor and head of the Laboratory of Molecular Neuro-Oncology at Rockefeller and investigator at HHMI.

RNA splicing is the process by which the initial RNA copy of a gene, known as pre-mRNA, is pieced together to produce a mature mRNA that codes for cellular proteins. In alternative splicing, different pieces of this pre-mRNA, called exons, are stitched together to produce different mRNAs, and thus different proteins. The exon can be spliced in or out in a binary, computer-like fashion. By regulating alternative splicing cells
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Source:Rockefeller University


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