AUF1 facilitates microRNA-mediated gene silencing.
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.
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Kyung-Won
KW
Min
Department of Physics and Astronomy, Institute of Applied Physics, National Center for Creative Research Initiatives, Seoul National University, Seoul 151-747, Korea.
Myung Hyun
MH
Jo
Department of Physics and Astronomy, Institute of Applied Physics, National Center for Creative Research Initiatives, Seoul National University, Seoul 151-747, Korea.
Soochul
S
Shin
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Sylvia
S
Davila
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Richard W
RW
Zealy
Department of Plastic Surgery, Seoul National University Bundang Hospital, Seongnam 13605, Korea.
Soo Im
SI
Kang
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Lawson T
LT
Lloyd
Department of Physics and Astronomy, Institute of Applied Physics, National Center for Creative Research Initiatives, Seoul National University, Seoul 151-747, Korea.
Sungchul
S
Hohng
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.|Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA.
Je-Hyun
JH
Yoon
D020413:3' Untranslated Regions / Q000235:genetics; D017398:Alternative Splicing; D060565:Argonaute Proteins / Q000378:metabolism; D001483:Base Sequence; D031541:Fluorescence Resonance Energy Transfer; D020868:Gene Silencing / Q000502:physiology*; D006367:HeLa Cells; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms; D034622:RNA Interference; D020871:RNA Stability / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism
D020413:3' Untranslated Regions; C466422:AGO2 protein, human; D060565:Argonaute Proteins; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D035683:MicroRNAs; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C487931:mirnlet7 microRNA, human