Scholarlink

<p>RNA modifications have emerged as crucial regulators of cellular processes linked to aging. However, the dynamic changes in global RNA modification patterns during aging and their functional implications remain underexplored. Here, we comprehensively deciphered the RNA modification landscapes of total RNA, poly(A)-enriched mRNA, and tRNA-enriched fragments across six tissues in both young and aged mice, as well as in multiple cellular senescence models. Aged tissues exhibit overall decline of RNA modification abundance in tRNA, rather than in total RNA or mRNA, when compared to young tissues. Correspondingly, the expression of tRNA methyltransferases, METTL1 and TRMT1, also declines with aging and senescence. Modulation of these methyltransferases affects cellular senescence phenotypes; specifically, Mettl1 depletion results in accelerated aging in mice. Mechanistically, fibroblasts are identified as the primary cell type responsible for the aging traits induced by Mettl1 deficiency in mice. Reduced m<sup>7</sup>G modification in fibroblasts leads to a decrease in the abundance of m<sup>7</sup>G-modified tRNAs, which in turn impairs translation efficiency and protein synthesis, and contributes to an accumulation of tRNA-derived small RNAs (tsRNAs). Remarkably, these alterations affected the translation of genes involved in senescence and aging pathways. Our study provides a comprehensive landscape of tRNA modifications during aging and demonstrates that decreased activity of METTL1 in fibroblasts drives aging. Thus, modulation of tRNA modifications may be a promising strategy for improving healthy aging and alleviating age-associated disorders.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Dynamic tRNA modification landscapes reveal METTL1 in fibroblasts as a central regulator of aging

  • 期刊论文

  • 发表日期：

    2026年6月24日

查看全文
  • Yan Zhu,
  • Xin Wang,
  • Yun Li,
  • Wenlin Jiang,
  • Zheng Wu,
  • San Xu,
  • Zixin Tan,
  • Aike Wu,
  • Yisheng Cai,
  • Yandi Yang,
  • Xin Xiao,
  • Xinwei Kuang,
  • Guangtong Deng,
  • Yiya Zhang,
  • Mengting Chen,
  • Ji Li,
  • Yunfang Zhang,
  • Zhili Deng

摘要

RNA modifications have emerged as crucial regulators of cellular processes linked to aging. However, the dynamic changes in global RNA modification patterns during aging and their functional implications remain underexplored. Here, we comprehensively deciphered the RNA modification landscapes of total RNA, poly(A)-enriched mRNA, and tRNA-enriched fragments across six tissues in both young and aged mice, as well as in multiple cellular senescence models. Aged tissues exhibit overall decline of RNA modification abundance in tRNA, rather than in total RNA or mRNA, when compared to young tissues. Correspondingly, the expression of tRNA methyltransferases, METTL1 and TRMT1, also declines with aging and senescence. Modulation of these methyltransferases affects cellular senescence phenotypes; specifically, Mettl1 depletion results in accelerated aging in mice. Mechanistically, fibroblasts are identified as the primary cell type responsible for the aging traits induced by Mettl1 deficiency in mice. Reduced m7G modification in fibroblasts leads to a decrease in the abundance of m7G-modified tRNAs, which in turn impairs translation efficiency and protein synthesis, and contributes to an accumulation of tRNA-derived small RNAs (tsRNAs). Remarkably, these alterations affected the translation of genes involved in senescence and aging pathways. Our study provides a comprehensive landscape of tRNA modifications during aging and demonstrates that decreased activity of METTL1 in fibroblasts drives aging. Thus, modulation of tRNA modifications may be a promising strategy for improving healthy aging and alleviating age-associated disorders.