Scientists Decode How a Protein on the Move Keeps Cells Healthy

Scientists are striving to gain a better understanding of the RNA interference mechanism, which might lead to improved cancer treatments. Researchers have uncovered how the Argonaute protein uses limited resources to keep protein creation on track. This discovery in fundamental science might pave the way for innovative new medicines in the future.

Proteins are manufactured by cells in the same way as they are manufactured by factories. However, if they generate too much at the wrong moment, illnesses like cancer might result, therefore they use RNA interference to regulate production (RNAi). RNAi is already being used to treat painful kidney and liver illnesses, with seven more medicines in clinical studies as of July 2021. RNAi medicines have a lot of promise, and researchers at Cold Spring Harbor Laboratory (CSHL) are working hard to get a full understanding of the process so that they may enhance current therapies and develop better ones in the future.

Leemor Joshua - Tor, a CSHL professor and HHMI researcher, and Brianna Bibel, a recent CSHL School of Biological Sciences graduate, are helping to fill in some of the gaps. They just found how Argonaute (Ago), an RNAi workhorse protein, manages to keep protein synthesis on track despite restricted resources.

Because RNAi is such a basic and widely utilized technique, Joshua-Tor believes it is critical to fully comprehend how it operates. It also serves as a form of therapeutic safety net because it does not create lasting cell alterations and may be reversed.

“For therapeutics, you’d kinda maybe not wanna mess around with the genome so much. In all these kinds of things, you wanna know exactly what’s happening, and if something isn’t working, then you know what to do and where to look. The more information you have, the better it is—you get a complete picture of what’s happening," Joshua-Tor explains.

Ago aids in the inhibition of protein synthesis by locating, binding, and deleting mRNA molecules, which instruct cells to produce proteins. However, the amount of Ago in the body is tiny compared to the amount of mRNA it needs to target. The protein can still find another after killing one, but it won't be able to do it without assistance. Bibel revealed how cells employ phosphorylation to weaken Ago's grasp on one mRNA target and let it to migrate to the next.

According to Bibel, “Our theory is that having phosphorylation promote release is a way that you could free up Argonaute because when the target gets released, the guide’s still there and it’s super duper stable. So our thinking is that by phosphorylating it, you’re going to free it to go repress other targets—because it’s still totally capable of doing that work.”

Bibel thinks that her discoveries will become useful as RNAi research proceeds.“A lot of great advances in science come from just doing basic research,” she remarked. “And this is one of those basic research questions, trying to figure out how this is working.”