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The tRNA methyltransferase NSun2 stabilizes p16INK4 mRNA by methylating the 3′-untranslated region of p16

Author

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  • Xiaotian Zhang

    (Research Center on Aging, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, PR China.)

  • Zhenyun Liu

    (Research Center on Aging, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, PR China.)

  • Jie Yi

    (Research Center on Aging, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, PR China.)

  • Hao Tang

    (Research Center on Aging, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, PR China.)

  • Junyue Xing

    (Research Center on Aging, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, PR China.)

  • Minqwei Yu

    (The First Clinical College, Wuhan University, 9 Ziyang Road, Wuhan 430060, PR China.)

  • Tanjun Tong

    (Research Center on Aging, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, PR China.)

  • Yongfeng Shang

    (Research Center on Aging, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, PR China.)

  • Myriam Gorospe

    (Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd., Baltimore, Maryland 21224, USA.)

  • Wengong Wang

    (Research Center on Aging, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, PR China.)

Abstract

The impact of methylation of the 3′-untranslated region (UTR) of a messenger RNA (mRNA) remains largely unknown. Here we show that NSun2, a transfer RNA methyltransferase, inhibits the turnover of p16INK4 mRNA. Knockdown of NSun2 reduces p16 expression by shortening the half-life of the p16 mRNA, while overexpression of NSun2 stabilizes the p16 mRNA. In vitro methylation assays show that NSun2 methylates the p16 3′UTR at A988. Knockdown of NSun2 reduces the stability of the EGFP-p16 chimeric reporter transcripts bearing wild-type p16 3′UTR, but not p16 3′UTR with a mutant methylation site. Methylation by NSun2 prevents the association of p16 3′UTR with HuR, AUF1 and Ago2/RISC, and prevents the recruitment of EGFP-p16 3′UTR chimeric transcripts to processing bodies. In response to oxidative stress, NSun2 is essential for elevating p16 expression levels. We conclude that NSun2-mediated methylation of the p16 3′UTR is a novel mechanism to stabilize p16 mRNA.

Suggested Citation

  • Xiaotian Zhang & Zhenyun Liu & Jie Yi & Hao Tang & Junyue Xing & Minqwei Yu & Tanjun Tong & Yongfeng Shang & Myriam Gorospe & Wengong Wang, 2012. "The tRNA methyltransferase NSun2 stabilizes p16INK4 mRNA by methylating the 3′-untranslated region of p16," Nature Communications, Nature, vol. 3(1), pages 1-12, January.
  • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1692
    DOI: 10.1038/ncomms1692
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