A large-scale analysis has confirmed how viruses use the host cell's ribonucleic acid (RNA) regulation system to keep their own RNA stable for longer. In the process, researchers also found new RNA regulatory elements that can increase the lifespan of messenger RNA (mRNA) and boost protein production.
The Ministry of Science and ICT said that a team led by V. Narry Kim of the Institute for Basic Science (IBS) RNA Research Center analyzed 337 vertebrate-infecting viruses and identified regulatory elements and mechanisms that enhance RNA stability. The findings were published in the international journal Cell on the 14th.
At the end of mRNA is a "poly(A) tail" made of consecutive adenines (A), and when this tail shortens, mRNA is easily degraded. Viruses are known to extend RNA lifespan by using host cell enzymes to protect or rebuild this tail.
The team divided the genomes of 337 virus species across 297 genera into about 200,000 RNA fragments for analysis. They identified 23 regulatory elements that harness the "TENT4" enzyme to create mixed tails at RNA ends and suppress degradation. These elements were found in 19 virus genera and were classified into at least six types by sequence and structure.
Researchers also discovered regulatory elements that operate differently from TENT4. "Pt1," identified in eel picornavirus, directly recruited PAP, the enzyme that makes poly(A) tails, to re-extend shortened tails. The team named such viral RNA elements that use host tail-regulating enzymes "tailons."
In experiments applying Pt1 to linear mRNA, the poly(A) tail length increased from 60 to as many as 194, and the mRNA half-life rose from 7.6 hours to 23.1 hours, roughly tripling. According to the researchers, the stability approached that of circular RNA, which resists degradation.
These results are meaningful because they present a way to extend lifespan while maintaining the relatively simple-to-manufacture linear mRNA form. They could be used to improve the duration and protein production efficiency of mRNA Vaccine and RNA-based therapeutics.
Director General V. Narry Kim said, "This study is a large-scale achievement that reveals the sophisticated strategies viruses use to exploit the host cell's RNA regulatory system," adding, "The identified regulatory elements will be powerful molecular tools that overcome the limits of existing mRNA therapy technologies and greatly increase the duration of drug efficacy."
References
Cell (2026), DOI: https://doi.org/10.1016/j.cell.2026.07.038