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AUF1 facilitates microRNA-mediated gene silencing
Kyung-Won Min1, Myung Hyun Jo2, Soochul Shin2
1Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Nucleic Acids Research
|March 24, 2017
Summary
AUF1 protein promotes microRNA (miRNA)-mediated gene silencing by influencing mRNA decay. AUF1 affects multiple steps in the RNA-induced silencing complex pathway, promoting global mRNA decay.
Area of Science:
- Molecular Biology
- Gene Regulation
- RNA Biology
Background:
- Eukaryotic mRNA decay is regulated by RNA-binding proteins (RBPs) and microRNAs (miRNAs).
- AU-binding factor 1 (AUF1) is an RBP with four isoforms, crucial for miRNA-mediated gene silencing.
- Previous work showed AUF1 facilitates miRNA loading to Argonaute 2 (AGO2).
Purpose of the Study:
- To investigate AUF1's role in miRNA-mediated mRNA decay.
- To elucidate AUF1's influence on the interaction between miRNAs and AGO2.
- To understand AUF1's impact on the kinetics of RNA-induced silencing complex assembly and function.
Main Methods:
- Depletion of AUF1 to assess global miRNA-AGO2 interactions.
- Single-molecule analysis to study complex assembly dynamics.
- mRNA abundance measurements upon AUF1 overexpression.
Main Results:
- AUF1 depletion abolished global miRNA-AGO2 interactions.
- AUF1 unexpectedly slowed the assembly of AGO2-let-7b-mRNA complexes.
- Overexpression of AUF1 led to decreased abundance of target mRNAs recognized by both miRNA and AUF1.
Conclusions:
- AUF1 plays a significant role in promoting miRNA-mediated mRNA decay.
- AUF1 influences multiple stages of the AGO2-miRNA-mediated decay pathway.
- AUF1 acts globally to promote mRNA decay in the context of miRNA regulation.
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