GSE112006
The genomic landscape of microRNA-target interactions in human cells
MicroRNAs play important roles in physiology and pathology by repressing target gene expression, but it remains challenging to identify targets and regulatory networks on a global scale. MicroRNAs often pair with targets complementary to nucleotide 2 to 7, but such complementarity is not always found within targets. Here we show global views of microRNA-target interactions with unparalleled resolution and confidence by conducting a series of UV-crosslinking and immunoprecipitation experiments for AGO2. Our data indicate that direct interactions are mainly guided by seed complementarity. However, we find that different microRNAs recognize atypical sites with varying tolerance to mismatches. Pathway enrichment analyses reveal that many target genes encoding constituents of the same pathways such as Hippo and Wnt, yet unexpectedly, both positive and negative components are targeted by identical and/or different microRNAs from a same polycistronic cluster. The prevalence of incoherent feedforward loops epitomizes the complexity of microRNA-target networks and the pitfalls of reductionistic inference of miRNA functions. Our results illuminate target sites of miRNAs and regulatory networks that facilitate a deeper understanding of miRNA functions. Overall design: CLIP-seq of endogenous AGO2 by using anti-AGO2-antibody (Proteintech) and IgG controls, sequencing of microRNAs associated with AGO2