RNA Cut-and-Paste Makes an Adult Heart

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Kirstie Saltsman

Much like we mix and match shirts, pants, and shoes to put together different outfits, a cell can shuffle segments of its genetic material to produce thousands of different, but related, proteins. This process, called alternative splicing, acts on RNA molecules that carry information from DNA to the cell’s protein-making machinery. In many cases, cells use alternative splicing to make particular proteins according to the circumstances: Just as you might choose to wear a raincoat on a soggy day, a cell can make a protein variant to suit its needs.

Now, basic researchers have discovered that alternative splicing appears to play a key role in the development of a healthy heart. Xiang-Dong Fu, Ph.D., of the University of California, San Diego, used genetic engineering technology to create mice that could not produce ASF/SF2, a protein known to be involved in cutting and pasting RNA. Although these experimental mice looked normal at birth, within a few weeks their hearts could not pump blood very well and they died soon thereafter. Fu discovered that, without the proper ASF/SF2 splicing tool, the mice made the wrong version of an important heart enzyme that helps transform a juvenile mouse heart into that of an adult. The enzyme, the scientists learned, has also been linked to heart attacks.

Fu’s findings may lead to a deeper understanding of alternative splicing in the normal development of body organs. The research may also shed light on why heart attacks occur and could suggest strategies to prevent them.