Dataset Information

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

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.

SUBMITTER: Chen Q

PROVIDER: S-EPMC10572189 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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A Novel tRNA-Derived Fragment, tRF<sup>GlnCTG</sup>, Regulates Angiogenesis by Targeting Antxr1 mRNA.

Chen Qiuyang Q Shen Linyuan L Liao Tianci T Qiu Yanhao Y Lei Yuhang Y Wang Xingyu X Chen Lei L Zhao Ye Y Niu Lili L Wang Yan Y Zhang Shunhua S Zhu Li L Gan Mailin M

International journal of molecular sciences 20230926 19

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<sup>GlnCTG</sup>) were found to be overexpressed in high abundance in the damaged muscle. Subsequent in vitro experiments revealed that the overexpr ...[more]

PMID: 37833999

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Project description:BackgroundMyopia has emerged as a major public health concern globally, which is tightly associated with scleral extracellular matrix (ECM) remodeling and choroidal vasculopathy. Choroidal vasculopathy has gradually been recognized as a critical trigger of myopic pathology. However, the precise mechanism controlling choroidal vasculopathy remains unclear. Transfer RNA-derived fragments (tRFs) are known as a novel class of small non-coding RNAs that plays important roles in several biological and pathological processes. In this study, we investigated the role of tRF-22-8BWS72092 (tRF-22) in choroidal vasculopathy and myopia progression.MethodsThe tRF-22 expression pattern under myopia-related stresses was detected by qRT-PCR. MTT assays, EdU incorporation assays, Transwell migration assays, and Matrigel assays were conducted to detect the role of tRF-22 in choroidal endothelial cell function in vitro. Isolectin B4 staining and choroidal sprouting assay ex vivo were conducted to detect the role of tRF-22 in choroidal vascular dysfunction in vivo. Immunofluorescent staining, western blot assays and ocular biometric parameters measurement were performed to examine whether altering tRF-22 expression in choroid affects scleral hypoxia and ECM remodeling and myopia progression in vivo. Bioinformatics analysis and luciferase activity assays were conducted to identify the downstream targets of tRF-22. RNA-sequencing combined with m6A-qPCR assays were used to identify the m6A modified targets of METTL3. Gain-of-function and Loss-of-function analysis were performed to reveal the mechanism of tRF-22/METTL3-mediated choroidal vascular dysfunction.ResultsThe results revealed that tRF-22 expression was significantly down-regulated in myopic choroid. tRF-22 overexpression alleviated choroidal vasculopathy and retarded the progression of myopia in vivo. tRF-22 regulated choroidal endothelial cell viability, proliferation, migration, and tube formation ability in vitro. Mechanistically, tRF-22 interacted with METTL3 and blocked m6A methylation of Axin1 and Arid1b mRNA transcripts, which led to increased expression of Axin1 and Arid1b.ConclusionsOur study reveals that the intervention of choroidal vasculopathy via tRF-22-METTL3- Axin1/Arid1b axis is a promising strategy for the treatment of patients with myopic pathology.

Dataset Information

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

Publications

A Novel tRNA-Derived Fragment, tRF<sup>GlnCTG</sup>, Regulates Angiogenesis by Targeting Antxr1 mRNA.

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Dataset Information

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

Publications

A Novel tRNA-Derived Fragment, tRF<sup>GlnCTG</sup>, Regulates Angiogenesis by Targeting Antxr1 mRNA.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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