Nakasone Award winner Kim V. Narry discovers viral mechanism that extends mRNA lifespan

IBS researchers found a viral mechanism that nearly tripled linear mRNA’s lifespan in cells, potentially improving vaccines and therapeutics.

Kim V. Narry, director of the Center for RNA Research at the Institute for Basic Science (IBS), poses for a photo during an interview with JoongAng Ilbo on March 10, 2023. JUN MIN-KYU

A research team led by Kim V. Narry, director of the Center for RNA Research at the Institute for Basic Science (IBS), has uncovered the mechanism that viruses use to regulate RNA, the Ministry of Science and ICT said Friday.

The team analyzed 337 viruses that infect vertebrates and found that they use RNA-regulating enzymes in host cells to protect their poly(A) tails.

The poly(A) tail at the end of messenger RNA, or mRNA, helps maintain its stability. Applying the mechanism to mRNA vaccines and therapeutics could improve their performance. While mRNA, also used in Covid-19 vaccines, has emerged as a promising platform for next-generation therapeutics, it is easily broken down by enzymes after entering the body.

The researchers found that an RNA regulatory element called Pt1 works differently from existing approaches. Rather than simply protecting the tail, it promotes synthesis of the poly(A) tail and extends it as it shortens. That continuous replenishment of the RNA tail slows the degradation of mRNA.

When Pt1 was applied to linear mRNA, its lifespan inside cells increased nearly three-fold, from 7.6 hours to 23.1 hours. The lifespan approached that of circular RNA, which is known as the most stable form of RNA.

An illustration of how tailons, RNA regulatory elements, work. Tailon sequences in mRNA bind to TENT4 or PAP proteins, which reinforce the mRNA’s poly(A) tail and stabilize the molecule. MINISTRY OF SCIENCE AND ICT

“The technology could serve as a foundation for improving the performance of mRNA vaccines and therapeutics, since it increases RNA lifespan and protein production while retaining the advantages of linear mRNA, which is easier to manufacture,” the research team said.

The findings were published in the journal Cell. Kim was also named the first Asian recipient of the Human Frontier Science Program’s (HFSP) Nakasone Award last month, in recognition of her achievements in mRNA research.