UPF1 helicase promotes TSN-mediated miRNA decay
| Autor: | Keita Miyoshi, Reyad A. Elbarbary, Lynne E. Maquat, Omar Hedaya, Jason R. Myers |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
RNA Stability urologic and male genital diseases Deep sequencing 03 medical and health sciences Cell Line Tumor Endoribonucleases microRNA Genetics Humans Messenger RNA Nuclease biology Urinary Bladder Cancer Sequence Analysis RNA High-Throughput Nucleotide Sequencing Helicase RNA Helicase A In vitro Cell biology DNA-Binding Proteins MicroRNAs HEK293 Cells 030104 developmental biology Urinary Bladder Neoplasms Trans-Activators biology.protein RNA Helicases Research Paper Developmental Biology |
| Zdroj: | Genes & Development. 31:1483-1493 |
| ISSN: | 1549-5477 0890-9369 |
| DOI: | 10.1101/gad.303537.117 |
| Popis: | While microRNAs (miRNAs) regulate the vast majority of protein-encoding transcripts, little is known about how miRNAs themselves are degraded. We recently described Tudor-staphylococcal/micrococcal-like nuclease (TSN)-mediated miRNA decay (TumiD) as a cellular pathway in which the nuclease TSN promotes the decay of miRNAs that contain CA and/or UA dinucleotides. While TSN-mediated degradation of either protein-free or AGO2-loaded miRNAs does not require the ATP-dependent RNA helicase UPF1 in vitro, we report here that cellular TumiD requires UPF1. Results from experiments using AGO2-loaded miRNAs in duplex with target mRNAs indicate that UPF1 can dissociate miRNAs from their mRNA targets, making the miRNAs susceptible to TumiD. miR-seq (deep sequencing of miRNAs) data reveal that the degradation of ∼50% of candidate TumiD targets in T24 human urinary bladder cancer cells is augmented by UPF1. We illustrate the physiological relevance by demonstrating that UPF1-augmented TumiD promotes the invasion of T24 cells in part by degrading anti-invasive miRNAs so as to up-regulate the expression of proinvasive proteins. |
| Databáze: | OpenAIRE |
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