The presence of a hydroxyl group at the 2'-position in its ribose makes RNA susceptible to hydrolysis. Stabilization of RNAs for storage, transport and biological application thus remains a serious challenge, particularly for larger RNAs that are not accessible by chemical synthesis. Here we present reversible 2'-OH acylation as a general strategy to preserve RNA of any length or origin. High-yield polyacylation of 2'-hydroxyls ('cloaking') by readily accessible acylimidazole reagents effectively shields RNAs from both thermal and enzymatic degradation. Subsequent treatment with water-soluble nucleophilic reagents removes acylation adducts quantitatively ('uncloaking') and recovers a remarkably broad range of RNA functions, including reverse transcription, translation and gene editing. Furthermore, we show that certain α-dimethylamino- and α-alkoxy- acyl adducts are spontaneously removed in human cells, restoring messenger RNA translation with extended functional half-lives. These findings support the potential of reversible 2'-acylation as a simple and general molecular solution for enhancing RNA stability and provide mechanistic insights for stabilizing RNA regardless of length or origin.

Linglan Fang

Lu Xiao

Yong Woong Jun

Yoshiyuki Onishi

Eric T Kool

Nature chemistry

NATURE CHEMISTRY 是一本月刊，致力于发表描述化学所有领域最重要和最前沿研究的高质量论文。除了反映分析化学、无机化学、有机化学和物理化学等传统核心学科外，该杂志还收录了广泛的化学研究，包括但不限于催化、计算和理论化学、环境化学、绿色化学、药物化学、核化学、高分子化学、超分子化学和表面化学。其他跨学科主题，如生物无机、生物有机、有机金属和物理-有机化学也将成为特色。还鼓励提交详细介绍在化学和其他科学探究领域（如生物学、材料科学、纳米技术和物理学）的界面进行的多学科研究的手稿，其中工作的中心主题——以及报告的主要进展——落在在化学的范围内。除了初级研究，《自然化学》还发表评论文章、新闻和观点、关于其他期刊报道的重要工作的研究亮点、评论、书评、通信以及实验室以外更广泛的化学图景的分析——包括教育、资金、政策、知识产权以及化学对社会的影响等问题。通过这种方式，该杂志旨在成为全球化学界的代言人。《自然化学》致力于通过公平和严格的审查过程发表化学各个领域的顶级原创研究。它为作者的论文提供高知名度、获得广泛的读者群、高标准的复制编辑和制作、快速出版以及独立于学术团体和其他既得利益者。

Nature Chemistry is a monthly journal dedicated to publishing high-quality research papers that describe the most important and cutting-edge studies across all areas of chemistry. In addition to reflecting traditional core disciplines such as analytical chemistry, inorganic chemistry, organic chemistry, and physical chemistry, the journal also includes a wide range of chemical research, including but not limited to catalysis, computational and theoretical chemistry, environmental chemistry, green chemistry, medicinal chemistry, nuclear chemistry, polymer chemistry, supramolecular chemistry, and surface chemistry. Other interdisciplinary topics, such as bioinorganic chemistry, bioorganic chemistry, organometallic chemistry, and physical-organic chemistry, will also be featured. We encourage the submission of manuscripts that detail multidisciplinary research at the interface of chemistry and other scientific inquiries (such as biology, materials science, nanotechnology, and physics), particularly those where the central theme of the work—and the main advancements reported—falls within the realm of chemistry. In addition to primary research, Nature Chemistry also publishes commentary articles, news and views, highlights of significant work reported in other journals, reviews, book reviews, correspondence, and analyses of the broader chemical landscape beyond the laboratory, including issues such as education, funding, policy, intellectual property, and the societal impact of chemistry. In this way, the journal aims to be a voice for the global chemistry community. Nature Chemistry is committed to publishing top-tier original research across all areas of chemistry through a fair and rigorous review process, providing high visibility for authors' papers, a broad readership, high standards of copyediting and production, rapid publication, and independence from academic societies and other vested interests.

《Nature Chemistry》是一本月刊，致力于发表化学各个领域最重要和前沿的高质量研究论文。该杂志不仅涵盖传统的分析化学、无机化学、有机化学和物理化学等核心学科，还涉及催化、计算与理论化学、环境化学、绿色化学、药物化学、核化学、高分子化学、超分子化学和表面化学等广泛的化学研究领域。此外，跨学科的主题，如生物无机化学、生物有机化学、有机金属化学和物理-有机化学，也将成为该杂志的特色之一。我们鼓励提交涉及化学与其他科学领域（如生物学、材料科学、纳米技术和物理学）交叉研究的手稿，特别是那些以化学为中心主题的多学科研究。除了原始研究，《Nature Chemistry》还刊登评论文章、新闻与观点、关于其他期刊重要研究的亮点、评论、书评、通信以及更广泛的化学领域分析，包括教育、资金、政策、知识产权及化学对社会影响等问题。通过这些方式，该杂志旨在成为全球化学界的代言人。《Nature Chemistry》致力于通过公平和严格的审查过程，发表化学各个领域的顶级原创研究，提供高知名度、广泛的读者群、高标准的编辑和制作、快速出版，并独立于学术团体和其他既得利益者。

Nature Chemistry

Nat Chem

Reversible 2'-OH acylation enhances RNA stability.

Reversible 2′-acylation is presented as a general strategy to preserve RNA of any length or origin and certain α-dimethylamino- and α-alkoxy- acyl adducts are spontaneously removed in human cells, restoring messenger RNA translation with extended functional half-lives.

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化学	1
化学, 化学综合	1

Reversible 2'-OH acylation enhances RNA stability.

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Category	Quartile
CHEMISTRY, MULTIDISCIPLINARY	1