A Novel Pathway of Functional microRNA Uptake and Mitochondria Delivery.

Autor: Liu J; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu, 210093, China., Li W; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu, 210093, China., Li J; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu, 210093, China., Song E; The Laboratory of Biological Electron Microscopy and Structural Biology Centre for Biological Imaging, Institute of Biophysics Chinese, Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing, 100101, China., Liang H; School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, Jiangsu, 211198, China., Rong W; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu, 210093, China., Jiang X; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu, 210093, China., Xu N; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu, 210093, China., Wang W; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu, 210093, China., Qu S; School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, Jiangsu, 211198, China., Gu S; Institute of Geriatric Medicine, Jiangsu Province Geriatric Hospital, Nanjing, Jiangsu, China., Zhang Y; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu, 210093, China., Yu Zhang C; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu, 210093, China., Zen K; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu, 210093, China.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2023 Aug; Vol. 10 (24), pp. e2300452. Date of Electronic Publication: 2023 Jun 25.
DOI: 10.1002/advs.202300452
Abstrakt: Extracellular microRNAs (miRNAs) play a critical role in horizontal gene regulation. Uptake of extracellular miRNAs by recipient cells and their intracellular transport, however, remains elusive. Here RNA phase separation is shown as a novel pathway of miRNA uptake. In the presence of serum, synthetic miRNAs rapidly self-assembly into ≈110 nm discrete nanoparticles, which enable miRNAs' entry into different cells. Depleting serum cationic proteins prevents the formation of such nanoparticles and thus blocks miRNA uptake. Different from lipofectamine-mediated miRNA transfection in which majority of miRNAs are accumulated in lysosomes of transfected cells, nanoparticles-mediated miRNA uptake predominantly delivers miRNAs into mitochondria in a polyribonucleotide nucleotidyltransferase 1(PNPT1)-dependent manner. Functional assays further show that the internalized miR-21 via miRNA phase separation enhances mitochondrial translation of cytochrome b (CYB), leading to increase in adenosine triphosphate (ATP) and reactive oxygen species (ROS) reduction in HEK293T cells. The findings thus reveal a previously unrecognized mechanism for uptake and delivery functional extracellular miRNAs into mitochondria.
(© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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