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An integrative platform for detection of RNA 2'-O-methylation reveals its broad distribution on mRNA.

ABSTRACT: Ribose 2'-O-methylation is involved in critical biological processes, but its biological functions and significance in mRNAs remain underexplored. We have developed NJU-seq, a sensitive method for unbiased 2'-O-methylation (Nm) profiling, and Nm-VAQ, a site-specific quantification tool. Using these tools in tandem, we identified thousands of Nm sites on mRNAs of human and mouse cell lines, of which 68 of 84 selected sites were further validated to be more than 1% 2'-O-methylated. Unlike rRNA, most mRNA Nm sites were from 1% to 30% methylated. In addition, mRNA Nm was dynamic, changing according to the circumstance. Furthermore, we show that fibrillarin is involved as a methyltransferase. By mimicking the detected Nm sites and the context sequence, the RNA fragments could be 2'-O-methylated and demonstrated higher stability but lower translation efficiency. Last, profiling of Nm sites in lung surgery samples revealed common signatures of lung cancer pathogenesis, providing potential new diagnostic markers.

SUBMITTER: Tang Y

PROVIDER: S-EPMC10985248 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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An integrative platform for detection of RNA 2'-O-methylation reveals its broad distribution on mRNA.

Tang Yao Y Wu Yifan Y Wang Sainan S Lu Xiaolan X Gu Xiangwen X Li Yong Y Yang Fan F Xu Ruilin R Wang Tao T Jiao Zichen Z Wu Yan Y Liu Liwei L Chen Jian-Qun JQ Wang Qiang Q Chen Qihan Q

Cell reports methods 20240306 3

Ribose 2'-O-methylation is involved in critical biological processes, but its biological functions and significance in mRNAs remain underexplored. We have developed NJU-seq, a sensitive method for unbiased 2'-O-methylation (Nm) profiling, and Nm-VAQ, a site-specific quantification tool. Using these tools in tandem, we identified thousands of Nm sites on mRNAs of human and mouse cell lines, of which 68 of 84 selected sites were further validated to be more than 1% 2'-O-methylated. Unlike rRNA, mo ...[more]

PMID: 38452769

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An integrative platform for detection of RNA 2'-O-methylation reveals its broad distribution on mRNA.

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An integrative platform for detection of RNA 2'-O-methylation reveals its broad distribution on mRNA.

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