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<p>Specialized ribosomes help determine which proteins are synthesized, however, the influence of age on ribosome heterogeneity and whether dysregulation of this process drives organismal aging is unknown. Here we examined the role of ribosomal RNA (rRNA) methylation in maintaining appropriate translation as organisms age. In a directed RNAi screen, we identified 18S rRNA N6’-dimethyl adenosine (m<sup>6,2</sup>A) methyltransferase, <i>dimt-1</i>, as a regulator of <i>C. elegans</i> lifespan and stress resistance. We demonstrate that DIMT-1 functions in the germline after mid-life to regulate lifespan. Depletion of <i>dimt-1</i> leads to selective translation of transcripts important for stress resistance and lifespan regulation in the <i>C. elegans</i> germline including the cytochrome P450 <i>daf-9</i>, which synthesizes a steroid that signals from the germline to the soma. <i>dimt-1</i> induced lifespan extension is dependent on the <i>daf-9</i> signaling pathway. Our findings highlight ribosome heterogeneity, and specific rRNA modifications, in maintaining appropriate translation later in life to promote healthy aging.</p>

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The 18S rRNA methyltransferase DIMT-1 regulates lifespan in the germline later in life

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月28日

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  • M. Hafiz Rothi,
  • Gautam Chandra Sarkar,
  • Joseph Al Haddad,
  • Wayne Mitchell,
  • Kejun Ying,
  • Nancy Pohl,
  • Roberto G. Sotomayor-Mena,
  • Julia Natale,
  • Scarlett Dellacona,
  • Vadim N. Gladyshev,
  • Eric Lieberman Greer

摘要

Specialized ribosomes help determine which proteins are synthesized, however, the influence of age on ribosome heterogeneity and whether dysregulation of this process drives organismal aging is unknown. Here we examined the role of ribosomal RNA (rRNA) methylation in maintaining appropriate translation as organisms age. In a directed RNAi screen, we identified 18S rRNA N6’-dimethyl adenosine (m6,2A) methyltransferase, dimt-1, as a regulator of C. elegans lifespan and stress resistance. We demonstrate that DIMT-1 functions in the germline after mid-life to regulate lifespan. Depletion of dimt-1 leads to selective translation of transcripts important for stress resistance and lifespan regulation in the C. elegans germline including the cytochrome P450 daf-9, which synthesizes a steroid that signals from the germline to the soma. dimt-1 induced lifespan extension is dependent on the daf-9 signaling pathway. Our findings highlight ribosome heterogeneity, and specific rRNA modifications, in maintaining appropriate translation later in life to promote healthy aging.