RNA Interference

K-State dairy professor discusses the use of RNA to turn off proteins.

by Shelby Mettlen, assistant editor

MANHATTAN, Kan. (June 15, 2016) — Nearly 20 years ago, the first RNA interference was discovered when researchers inserted double-stranded messenger RNA (mRNA) into young and developing Caenorhabditis elegans (C. elegans). The nematode, similar to a roundworm found in cattle, responded to the insertion of mRNA by twitching uncontrollably. What researchers ultimately found was that the result of this “twitcher” phenotype was the elimination of a protein that regulated muscle contraction.

The double-stranded RNA induced knockdown of the protein that regulates muscle contraction, explained Barry Bradford on June 15 at the annual Beef Improvement Federation symposium. By 2006, this discovery warranted its founders the Nobel Prize.

Bradford, professor of dairy cattle metabolic physiology at Kansas State University, described how RNA interference, or the insertion of double-stranded mRNA into a cell can “knock down” or essentially switch off certain proteins in an organism. He explained the relatively newly discovered micro RNA, or miRNA, and ways it can intentionally or unintentionally switch off proteins to cause new or different phenotypes.

His cornerstone example was double muscling, a trait found in Texel sheep. In these sheep, a mutation led to a new RNA binding site that aligned with miRNA that is highly expressed in muscle. This resulted in more knock down of the protein myostatin by the miRNA, minimizing the protein’s ability to limit muscle growth.

“My point is that this biological mechanism might actually be the key behind some of these really obvious phenotypic differences that we’ve seen in some of these breeds for hundreds of years,” Bradford said.

His hope is that the use of this mechanism can work to allow researchers and producers “help animals be more productive” through what Bradford calls a “next-generation pharmaceutical tool.”

The mechanism is also being used to produce genetically engineered foods, like the Arctic apple, which delays becoming brown after being cut for longer than traditionally grown apples.

The technology is also being used in human medicine.

“The exciting thing is, in the last six months, the first Phase 3 human clinical trial with an RNA interference therapeutic has finally come on board,” he explained, describing that the use of the mechanism is being researched to treat amyloidosis, a disease that causes nerve malfunction.

Where RNA interference shines with potential in the animal ag industry is in lactating cattle, Bradford said.

After a cow calves, the liver will appear to decrease in functionality. The cow loses her appetite due to complications like ketosis and even displaced abomasum. If researchers can pinpoint the gene that is causing this decrease in liver function, they can inject miRNA to turn off that protein for an amount of time to allow the cow’s liver to function properly while her calf is weaned.

There is much research to be done, he added, but the future is bright for RNA interference in cattle. 

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