AUF1 facilitates microRNA-mediated gene silencing

• Kyung-Won Min ^[1] ; Myung Hyun Jo ^[2] ; Soochul Shin ^[2] ; Sylvia Davila ^[1] ; Richard W. Zealy ^[1] ; Soo Im Kang ^[3] ; Lawson T. Lloyd ^[1] ; Sungchul Hohng ^[2] ; Je-Hyun Yoon ^[1]
  1. [1] Medical University of South Carolina

     Medical University of South Carolina

     Estados Unidos

     
  2. [2] Institute of Applied Physics

     Institute of Applied Physics

     Rusia

     
  3. [3] Seoul National University

     Seoul National University

     Corea del Sur

     

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• Localización: Nucleic acids research, ISSN 0305-1048, Vol. 45, Nº. 10, 2017, págs. 6064-6073
• Idioma: inglés
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  • Eukaryotic mRNA decay is tightly modulated by RNA-binding proteins (RBPs) and microRNAs (miRNAs). RBP AU-binding factor 1 (AUF1) has four isoforms resulting from alternative splicing and is critical for miRNA-mediated gene silencing with a distinct preference of target miRNAs. Previously, we have shown that AUF1 facilitates miRNA loading to Argonaute 2 (AGO2), the catalytic component of the RNA-induced silencing complex. Here, we further demonstrate that depletion of AUF1 abolishes the global interaction of miRNAs and AGO2. Single-molecule analysis revealed that AUF1 slowed down assembly of AGO2–let-7b–mRNA complex unexpectedly. However, target mRNAs recognized by both miRNA and AUF1 are less abundant upon AUF1 overexpression implying that AUF1 is a decay-promoting factor influencing multiple steps in AGO2–miRNA-mediated mRNA decay. Our findings indicate that AUF1 functions in promoting miRNA-mediated mRNA decay globally.