非编码 RNA Terc-53 和透明质酸受体 Hmmr 可调节小鼠的衰老。

IF 13.6 1区 生物学 Q1 CELL BIOLOGY
Sipeng Wu, Yiqi Cai, Lixiao Zhang, Xiang Li, Xu Liu, Guangkeng Zhou, Hongdi Luo, Renjian Li, Yujia Huo, Zhirong Zhang, Siyi Chen, Jinliang Huang, Jiahao Shi, Shanwei Ding, Zhe Sun, Zizhuo Zhou, Pengcheng Wang, Geng Wang
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引用次数: 0

摘要

衰老领域的一个基本问题是,低等无脊椎动物和哺乳动物的衰老是否存在本质区别。低等无脊椎动物与哺乳动物之间的一个主要区别是非编码 RNA 的丰富程度,其中大部分并不保守。我们之前发现了一种非编码 RNA Terc-53,它来自端粒酶的 RNA 成分 Terc。为了研究它的生理功能,我们在野生型和早期衰老的 Terc-/- 背景下生成了两种过表达该 RNA 的转基因小鼠模型。Terc-53小鼠表现出与年龄相关的认知能力下降和寿命缩短,尽管没有观察到早期发育缺陷或生理异常,这表明它参与了哺乳动物的正常衰老。随后的机理研究发现,透明质酸介导的运动受体(Hmmr)是 Terc-53 的主要作用因子。Terc-53 介导了 Hmmr 的降解,导致受影响组织的炎症加剧,加速了机体老化。通过 AAV 向海马补充 Hmmr 逆转了 Terc-53 转基因小鼠认知能力的下降。Terc-53和Hmmr在优雅小鼠中都没有同源物。节肢动物也不表达透明质酸(Stern,2017 年)。这些发现表明了哺乳动物衰老的复杂性,并为探索非编码 RNA 和 Hmmr 作为治疗与年龄相关的身体缺陷和改善健康寿命的手段开辟了新的道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Noncoding RNA Terc-53 and hyaluronan receptor Hmmr regulate ageing in mice.

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.

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来源期刊
Protein & Cell
Protein & Cell CELL BIOLOGY-
CiteScore
24.00
自引率
0.90%
发文量
1029
审稿时长
6-12 weeks
期刊介绍: Protein & Cell is a monthly, peer-reviewed, open-access journal focusing on multidisciplinary aspects of biology and biomedicine, with a primary emphasis on protein and cell research. It publishes original research articles, reviews, and commentaries across various fields including biochemistry, biophysics, cell biology, genetics, immunology, microbiology, molecular biology, neuroscience, oncology, protein science, structural biology, and translational medicine. The journal also features content on research policies, funding trends in China, and serves as a platform for academic exchange among life science researchers.
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