安定RNAエレメントがmRNA治療薬の新たな可能性を開く(Stable RNA Elements Open New Possibilities for mRNA Therapeutics)

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2026-08-14 韓国基礎科学研究院(IBS)

韓国・基礎科学研究院(IBS)の金(V. Narry Kim)センター長らの研究チームは、ウイルス由来の短いRNA配列がmRNAの安定性を大幅に向上させ、タンパク質産生を増強することを発見した。研究成果はCell誌に掲載された。研究では337種類の脊椎動物感染ウイルスのゲノムを約20万個の断片に分割して解析し、mRNAの安定化や翻訳促進に寄与する多数のRNA配列を同定した。研究チームはこれらを「Tailon(テイロン)」と命名した。多くのTailonは細胞内酵素TENT4を利用してポリ(A)テールを延長し、mRNA分解を抑制する。また、特に強力なPt1配列はPAPγやPAPαを直接動員してポリ(A)テールを伸長する新規機構を示した。Pt1を組み込んだ直鎖状mRNAの半減期は23.1時間となり、環状RNA(24.9時間)に匹敵した。さらにマウス実験では、Tailon搭載mRNAは従来型mRNAや環状RNAより高いタンパク質産生を示し、その効果は最大2週間持続した。今回の成果は、mRNAワクチンやがん免疫療法、タンパク質補充療法などにおいて、より少ない投与量で長期間効果を発揮する次世代mRNA医薬の開発につながる可能性がある。

安定RNAエレメントがmRNA治療薬の新たな可能性を開く(Stable RNA Elements Open New Possibilities for mRNA Therapeutics)
Figure 1. The researchers divided the genomes of vertebrate-infecting viruses into approximately 200-nucleotide segments, generating nearly 200,000 RNA fragments. Each fragment was introduced into cells in a construct expressing mRNA, and the researchers measured mRNA stability and protein synthesis efficiency.

<関連情報>

脊椎動物ウイルスRNAのRNA安定化と翻訳促進に関わる要素の機能アトラス Functional atlas of vertebrate viral RNA elements that stabilize RNA and enhance translation

Jenny J. Seo ∙ Chemin Lee ∙ Dongbin Lim ∙ Minseok Jeong ∙ Soo-Jin Jung ∙ V. Narry Kim
Cell  Published:August 13, 2026
DOI:https://doi.org/10.1016/j.cell.2026.07.038

Highlights

  • MPRA maps functional RNA elements across 297 vertebrate viral genera
  • Six distinct classes of TENT4-dependent elements reveal convergent viral evolution
  • Pt1, a TENT4-independent element, endows linear mRNAs with circRNA-like stability
  • Pt1 directly recruits canonical PAPs to promote cytoplasmic polyadenylation

Summary

Viruses encode diverse regulatory elements, but their breadth and mechanisms remain poorly defined. To address this gap, we performed massively parallel reporter assays spanning ∼200,000 genomic segments from 297 vertebrate-infecting viral genera. We identified numerous viral elements that enhance RNA stability and translation through TENT4-mediated mixed tailing, distributed across 19 genera and grouped into six distinct subclasses, indicating extensive convergent evolution. We also found diverse TENT4-independent elements acting through alternative pathways. One such element, Pt1 from Potamipivirus, stabilizes linear mRNA to levels comparable to circular RNA, suggesting its potential for RNA therapeutics. Pt1 directly recruits canonical poly(A) polymerases (PAPγ/α)—previously thought to function exclusively in transcription-coupled nuclear pre-mRNA processing—to drive cytoplasmic polyadenylation. Together, these findings chart the rich landscape of viral regulation, extend the scope of poly(A)-tail biology, and establish the virome as a valuable source for uncovering host RNA regulatory mechanisms.

細胞遺伝子工学
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