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Genes Dev. 2015 Aug 1;29(15):1599-604. doi: 10.1101/gad.263749.115.

AUF1 promotes let-7b loading on Argonaute 2.

Author information

1
Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA;
2
Department of Physics and Astronomy, Institute of Applied Physics, National Center for Creative Research Initiatives, Seoul National University, Seoul 151-747, Korea;
3
Department of Biochemistry and Molecular Biology, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
4
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases-Intramural Research Program, National Institutes of Health, Bethesda, Maryland 20892, USA;
5
Cancer Metastasis Control Center, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-338, Korea;
6
Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, Rockefeller University, New York, New York 10065, USA.

Abstract

Eukaryotic gene expression is tightly regulated post-transcriptionally by RNA-binding proteins (RBPs) and microRNAs. The RBP AU-rich-binding factor 1 (AUF1) isoform p37 was found to have high affinity for the microRNA let-7b in vitro (Kd = ∼ 6 nM) in cells. Ribonucleoprotein immunoprecipitation, in vitro association, and single-molecule-binding analyses revealed that AUF1 promoted let-7b loading onto Argonaute 2 (AGO2), the catalytic component of the RNA-induced silencing complex (RISC). In turn, AGO2-let-7 triggered target mRNA decay. Our findings uncover a novel mechanism by which AUF1 binding and transfer of microRNA let-7 to AGO2 facilitates let-7-elicited gene silencing.

KEYWORDS:

Argonaute; RISC; hnRNP D; microRNA; ribonucleoprotein complex

PMID:
26253535
PMCID:
PMC4536308
DOI:
10.1101/gad.263749.115
[Indexed for MEDLINE]
Free PMC Article

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