AUF1 promotes let-7b loading on Argonaute 2.

Genes & development (2015-08-09)
Je-Hyun Yoon, Myung Hyun Jo, Elizabeth J F White, Supriyo De, Markus Hafner, Beth E Zucconi, Kotb Abdelmohsen, Jennifer L Martindale, Xiaoling Yang, William H Wood, Yu Mi Shin, Ji-Joon Song, Thomas Tuschl, Kevin G Becker, Gerald M Wilson, Sungchul Hohng, Myriam Gorospe
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.

MATERIALS
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