RNA transcripts are subject to posttranscriptional gene regulation involving 
hundreds of RNA-binding proteins (RBPs) and microRNA-containing 
ribonucleoprotein complexes (miRNPs) expressed in a cell-type dependent fashion. 
We developed a cell-based crosslinking approach to determine at high resolution 
and transcriptome-wide the binding sites of cellular RBPs and miRNPs. The 
crosslinked sites are revealed by thymidine to cytidine transitions in the cDNAs 
prepared from immunopurified RNPs of 4-thiouridine-treated cells. We determined 
the binding sites and regulatory consequences for several intensely studied RBPs 
and miRNPs, including PUM2, QKI, IGF2BP1-3, AGO/EIF2C1-4 and TNRC6A-C. Our study 
revealed that these factors bind thousands of sites containing defined sequence 
motifs and have distinct preferences for exonic versus intronic or coding versus 
untranslated transcript regions. The precise mapping of binding sites across the 
transcriptome will be critical to the interpretation of the rapidly emerging 
data on genetic variation between individuals and how these variations 
contribute to complex genetic diseases.