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UPF1 helicase promotes TSN-mediated miRNA decay
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 promo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588929/ https://www.ncbi.nlm.nih.gov/pubmed/28827400 http://dx.doi.org/10.1101/gad.303537.117 |
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author | Elbarbary, Reyad A. Miyoshi, Keita Hedaya, Omar Myers, Jason R. Maquat, Lynne E. |
author_facet | Elbarbary, Reyad A. Miyoshi, Keita Hedaya, Omar Myers, Jason R. Maquat, Lynne E. |
author_sort | Elbarbary, Reyad A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5588929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-55889292018-01-15 UPF1 helicase promotes TSN-mediated miRNA decay Elbarbary, Reyad A. Miyoshi, Keita Hedaya, Omar Myers, Jason R. Maquat, Lynne E. Genes Dev Research Paper 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. Cold Spring Harbor Laboratory Press 2017-07-15 /pmc/articles/PMC5588929/ /pubmed/28827400 http://dx.doi.org/10.1101/gad.303537.117 Text en © 2017 Elbarbary et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Paper Elbarbary, Reyad A. Miyoshi, Keita Hedaya, Omar Myers, Jason R. Maquat, Lynne E. UPF1 helicase promotes TSN-mediated miRNA decay |
title | UPF1 helicase promotes TSN-mediated miRNA decay |
title_full | UPF1 helicase promotes TSN-mediated miRNA decay |
title_fullStr | UPF1 helicase promotes TSN-mediated miRNA decay |
title_full_unstemmed | UPF1 helicase promotes TSN-mediated miRNA decay |
title_short | UPF1 helicase promotes TSN-mediated miRNA decay |
title_sort | upf1 helicase promotes tsn-mediated mirna decay |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588929/ https://www.ncbi.nlm.nih.gov/pubmed/28827400 http://dx.doi.org/10.1101/gad.303537.117 |
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