We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Perturbation of METTL1-mediated tRNA N<sup>7</sup>- methylguanosine modification induces senescence and aging.
- Authors
Fu, Yudong; Jiang, Fan; Zhang, Xiao; Pan, Yingyi; Xu, Rui; Liang, Xiu; Wu, Xiaofen; Li, Xingqiang; Lin, Kaixuan; Shi, Ruona; Zhang, Xiaofei; Ferrandon, Dominique; Liu, Jing; Pei, Duanqing; Wang, Jie; Wang, Tao
- Abstract
Cellular senescence is characterized by a decrease in protein synthesis, although the underlying processes are mostly unclear. Chemical modifications to transfer RNAs (tRNAs) frequently influence tRNA activity, which is crucial for translation. We describe how tRNA N7-methylguanosine (m7G46) methylation, catalyzed by METTL1-WDR4, regulates translation and influences senescence phenotypes. Mettl1/Wdr4 and m7G gradually diminish with senescence and aging. A decrease in METTL1 causes a reduction in tRNAs, especially those with the m7G modification, via the rapid tRNA degradation (RTD) pathway. The decreases cause ribosomes to stall at certain codons, impeding the translation of mRNA that is essential in pathways such as Wnt signaling and ribosome biogenesis. Furthermore, chronic ribosome stalling stimulates the ribotoxic and integrative stress responses, which induce senescence-associated secretory phenotype. Moreover, restoring eEF1A protein mitigates senescence phenotypes caused by METTL1 deficiency by reducing RTD. Our findings demonstrate that tRNA m7G modification is essential for preventing premature senescence and aging by enabling efficient mRNA translation. The heterodimer of METTL1-WDR4 is responsible for adding methylation group to the N7 atom of guanine (m7G) in tRNA molecules. Here the authors show how the tRNA m7G modification mediates tRNA stability to control proteostasis by maintaining efficient protein synthesis, which is important for preventing premature senescence and aging.
- Subjects
TRANSFER RNA; RNA modification &; restriction; CELLULAR aging; PREMATURE aging (Medicine); GENETIC translation; ORGANELLE formation
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-49796-8