TY  - JOUR
A1  - Li, Jingjing
A1  - Kim, TaeHyung
A1  - Nutiu, Razvan
A1  - Ray, Debashish
A1  - Hughes, Timothy R.
A1  - Zhang, Zhaolei
T1  - Identifying mRNA sequence elements for target recognition by human Argonaute proteins
Y1  - 2014/05/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 775 
EP  - 785 
DO  - 10.1101/gr.162230.113 
VL  - 24 
IS  - 5 
UR  - http://genome.cshlp.org/content/24/5/775.abstract 
N2  - It is commonly known that mammalian microRNAs (miRNAs) guide the RNA-induced silencing complex (RISC) to target mRNAs through the seed-pairing rule. However, recent experiments that coimmunoprecipitate the Argonaute proteins (AGOs), the central catalytic component of RISC, have consistently revealed extensive AGO-associated mRNAs that lack seed complementarity with miRNAs. We herein test the hypothesis that AGO has its own binding preference within target mRNAs, independent of guide miRNAs. By systematically analyzing the data from in vivo cross-linking experiments with human AGOs, we have identified a structurally accessible and evolutionarily conserved region (∼10 nucleotides in length) that alone can accurately predict AGO–mRNA associations, independent of the presence of miRNA binding sites. Within this region, we further identified an enriched motif that was replicable on independent AGO-immunoprecipitation data sets. We used RNAcompete to enumerate the RNA-binding preference of human AGO2 to all possible 7-mer RNA sequences and validated the AGO motif in vitro. These findings reveal a novel function of AGOs as sequence-specific RNA-binding proteins, which may aid miRNAs in recognizing their targets with high specificity. 
ER  -