A novel method for stabilizing microRNA mimics

Biochemical and Biophysical Research Communications
Takuto NogimoriShin-Ichi Hoshino

Abstract

MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression at post-transcriptional level via translational repression and/or mRNA degradation. miRNAs are associated with many cellular processes, and down-regulation of miRNAs causes numerous diseases including cancer, neurological disorders, inflammation, and cardiovascular diseases, for which miRNA replacement therapy has emerged as a promising approach. This approach aims to restore down-regulated miRNAs using synthetic miRNA mimics. However, it remains a critical issue that miRNA mimics are unstable and transient in cells. Here, we first show that miRNA mimics are rapidly degraded by a mechanism different from Tudor-staphylococcal/micrococcal-like nuclease (TSN)-mediated miRNA decay, which degrades endogenous miRNAs, and newly identified 2'-5'-oligoadenylate synthetase (OAS)/RNase L as key factors responsible for the degradation of miRNA mimics in human cells. Our results suggest that the OAS1 recognizes miRNA mimics and produces 2'-5'-oligoadenylates (2-5A), which leads to the activation of latent endoribonuclease RNase L to degrade miRNA mimics. A small-molecule inhibitor that blocks RNase L can stabilize miRNA mimics. These findings pr...Continue Reading

Citations

Nov 5, 2019·Journal of Cellular Biochemistry·Yuzhuo WangMin Hu
Oct 2, 2019·Frontiers in Pharmacology·Nadezhda Mironova, Valentin Vlassov
Sep 11, 2020·International Journal of Molecular Sciences·Linsey J F PetersEmiel P C van der Vorst
Jul 20, 2021·Archives of Virology·Jiulue HuHamed Serati-Nouri
Aug 10, 2021·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Elayaraja KolanthaiSudipta Seal
Jan 19, 2022·Journal of Cosmetic Dermatology·Zhigang ZhangLechun Lyu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiovascular Inflammation

Inflammation plays a significant role in the development of cardiovascular diseases, an understanding of these endogenous processes is critical for evaluating the risks and potential treatment strategies. Discover the latest research on cardiovascular inflammation here.

Related Papers

Methods : a Companion to Methods in Enzymology
Reyad A Elbarbary, Lynne E Maquat
Epigenetics : Official Journal of the DNA Methylation Society
Nicholas C HoffendThomas B Tomasi
© 2022 Meta ULC. All rights reserved