UPF1 helicase promotes TSN-mediated miRNA decay

Reyad A. Elbarbary, Keita Miyoshi, Omar Hedaya, Jason R. Myers, Lynne E. Maquat

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1483-1493
Number of pages11
JournalGenes and Development
Volume31
Issue number14
DOIs
StatePublished - Jan 1 2017

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

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    Elbarbary, R. A., Miyoshi, K., Hedaya, O., Myers, J. R., & Maquat, L. E. (2017). UPF1 helicase promotes TSN-mediated miRNA decay. Genes and Development, 31(14), 1483-1493. https://doi.org/10.1101/gad.303537.117