All mRNA molecules are subject to some degree of post-transcriptional gene 
regulation (PTGR) involving sequence-dependent modulation of splicing, cleavage 
and polyadenylation, editing, transport, stability, and translation. The recent 
introduction of deep-sequencing technologies enabled the development of new 
methods for broadly mapping interaction sites between RNA-binding proteins 
(RBPs) and their RNA target sites. In this article, we review crosslinking and 
immunoprecipitation (CLIP) methods adapted for large-scale identification of 
target RNA-binding sites and the respective RNA recognition elements. CLIP 
methods have the potential to detect hundreds of thousands of binding sites in 
single experiments although the separation of signal from noise can be 
challenging. As a consequence, each CLIP method has developed different 
strategies to distinguish true targets from background. We focus on 
photoactivatable ribonucleoside-enhanced CLIP, which relies on the intracellular 
incorporation of photoactivatable ribonucleoside analogs into nascent 
transcripts, and yields characteristic sequence changes upon crosslinking that 
facilitate the separation of signal from noise. The precise knowledge of the 
position and distribution of binding sites across mature and primary mRNA 
transcripts allows critical insights into cellular localization and regulatory 
function of the examined RBP. When coupled with other systems-wide approaches 
measuring transcript and protein abundance, the generation of high-resolution 
RBP-binding site maps across the transcriptome will broaden our understanding of 
PTGR and thereby lead to new strategies for therapeutic treatment of genetic 
diseases perturbing these processes.