1. Academic Validation
  2. Noncoding RNA Terc-53 and hyaluronan receptor Hmmr regulate ageing in mice

Noncoding RNA Terc-53 and hyaluronan receptor Hmmr regulate ageing in mice

  • Protein Cell. 2024 May 9:pwae023. doi: 10.1093/procel/pwae023.
Sipeng Wu 1 Yiqi Cai 1 Lixiao Zhang 1 Xiang Li 1 Xu Liu 1 Guangkeng Zhou 1 Hongdi Luo 1 Renjian Li 1 Yujia Huo 1 Zhirong Zhang 1 Siyi Chen 1 Jinliang Huang 2 Jiahao Shi 1 Shanwei Ding 1 Zhe Sun 1 Zizhuo Zhou 1 Pengcheng Wang 1 Geng Wang 1
Affiliations

Affiliations

  • 1 State Key laboratory for Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, 361102 Xiamen, China.
  • 2 School of Life Sciences, Tsinghua University, Beijing 100084, China.
Abstract

One of the basic questions in the ageing field is whether there is fundamental difference between the ageing of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of Telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-ageing Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at early age was observed, indicating its involvement in normal ageing of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal ageing. AAV-delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan (Stern 2017). These findings demonstrate the complexity of ageing in mammals, and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.

Keywords

TERC-53; brain aging; mitochondrial noncoding RNAs; neuroinflammation; ubiquitination.

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