A novel method for stabilizing microRNA mimics
Autor: | Shin-ichi Hoshino, Koichi Ogami, Kazuya Furutachi, Takuto Nogimori, Nao Hosoda |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
RNase P RNA Stability Endoribonuclease Biophysics Endogeny Inflammation Biology Biochemistry 03 medical and health sciences 0302 clinical medicine Endoribonucleases microRNA Gene expression 2' 5'-Oligoadenylate Synthetase medicine Humans Molecular Biology Nuclease Mechanism (biology) Cell Biology Cell biology MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis biology.protein medicine.symptom HeLa Cells |
Zdroj: | Biochemical and Biophysical Research Communications. 511:422-426 |
ISSN: | 0006-291X |
Popis: | 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 provide a promising method for the stabilization of miRNA mimics, as well as for the efficient miRNA replacement therapy. |
Databáze: | OpenAIRE |
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