mTORC1-Rps15 Axis Contributes to the Mechanisms Underlying Global Translation Reduction During Senescence of Mouse Embryonic Fibroblasts

Su Wu; Siyao Xu; Ruofei Li; Kecheng Li; Xiaoqin Zhong; Yingying Li; Zhifen Zhou; Yi Liu; Ran Feng; Jianfei Zheng; Zhou Songyang; Feng Liu

doi:10.3389/fcell.2019.00337

mTORC1-Rps15 Axis Contributes to the Mechanisms Underlying Global Translation Reduction During Senescence of Mouse Embryonic Fibroblasts

Front Cell Dev Biol. 2019 Dec 11:7:337. doi: 10.3389/fcell.2019.00337. eCollection 2019.

Authors

Su Wu¹, Siyao Xu¹, Ruofei Li¹, Kecheng Li¹, Xiaoqin Zhong¹, Yingying Li¹, Zhifen Zhou¹, Yi Liu¹, Ran Feng¹, Jianfei Zheng¹, Zhou Songyang¹, Feng Liu¹

Affiliation

¹ MOE Key Laboratory of Gene Function and Regulation, Institute of Healthy Aging Research, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

Abstract

The reduction of protein translation is a common feature in senescent cells and aging organisms, yet the underlying mechanisms are not fully understood. Here we show that both global mRNA translation and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) kinase activity are declined in a senescent model of mouse embryonic fibroblasts (MEFs). Furthermore, RNA-seq analyses from polysomal versus total mRNA fractions identify TOP-like mRNA of Rps15 whose translation is regulated by mTORC1 during MEF senescence. Overexpression of Rps15 delays MEF senescence, possibly through regulating ribosome maturation. Together, these findings indicate that the activation of mTORC1-Rps15 axis ameliorate senescence by regulating ribosome biogenesis, which may provide further insights into aging research.

Keywords: MEF; Rps15; cell senescence; mRNA translation; mTORC1.