A Novel tRNA-Derived Fragment, tRFGlnCTG, Regulates Angiogenesis by Targeting Antxr1 mRNA

Qiuyang Chen; Linyuan Shen; Tianci Liao; Yanhao Qiu; Yuhang Lei; Xingyu Wang; Lei Chen; Ye Zhao; Lili Niu; Yan Wang; Shunhua Zhang; Li Zhu; Mailin Gan

doi:10.3390/ijms241914552

A Novel tRNA-Derived Fragment, tRF^GlnCTG, Regulates Angiogenesis by Targeting Antxr1 mRNA

Int J Mol Sci. 2023 Sep 26;24(19):14552. doi: 10.3390/ijms241914552.

Authors

Qiuyang Chen^{1

2}, Linyuan Shen^{1

2}, Tianci Liao^{1

2}, Yanhao Qiu^{1

2}, Yuhang Lei^{1

2}, Xingyu Wang^{1

2}, Lei Chen^{1

2}, Ye Zhao^{1

2}, Lili Niu^{1

2}, Yan Wang^{1

2}, Shunhua Zhang^{1

2}, Li Zhu^{1

2}, Mailin Gan^{1

2}

Affiliations

¹ Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
² Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, China.

Abstract

As a novel non-coding RNA with important functions corresponding to various cellular stresses, the function of tRFs in angiogenesis remains unclear. Firstly, small RNA sequencing was performed on normal and post-muscle injury mouse tibialis anterior muscle to identify and analyse differentially expressed tRF/tiRNA. tRNA GlnCTG-derived fragments (tRF^GlnCTG) were found to be overexpressed in high abundance in the damaged muscle. Subsequent in vitro experiments revealed that the overexpression of tRF^GlnCTG suppressed the vascular endothelial cells' viability, cell cycle G1/S transition, proliferation, migration, and tube-formation capacity. Similarly, in vivo experiments showed that the tRF^GlnCTG decreased the relative mRNA levels of vascular endothelial cell markers and pro-angiogenic factors and reduced the proportion of CD31-positive cells. Finally, luciferase activity analysis confirmed that the tRF^GlnCTG directly targeted the 3'UTR of Antxr1, leading to a significant reduction in the mRNA expression of the target gene. These results suggest that tRF^GlnCTG is a key regulator of vascular endothelial cell function. The results provide a new idea for further exploration of the molecular mechanisms that regulate angiogenesis.

Keywords: Antxr1; C166 cells; angiogenesis; proliferation; tRNA-derived fragment.

MeSH terms

Animals
Base Sequence
Endothelial Cells* / metabolism
Mice
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Transfer* / genetics
RNA, Transfer* / metabolism

Substances

RNA, Messenger
RNA, Transfer

Abstract

MeSH terms

Substances

Grants and funding