The human transcriptome is enriched for miRNA-binding sites located in cooperativity-permitting distance

摘要: MiRNAs are short, non-coding RNAs that regulate gene expression post-transcriptionally through specific binding to mRNA. Deregulation of miRNAs is associated with various diseases and interference miRNA function has proven therapeutic potential. Most mRNAs thought be regulated by multiple there some evidence such joint activity enhanced if a short distance between sites allows for cooperative binding. Until now, however, the concept cooperativity among not been addressed in transcriptome-wide approach. Here, we computationally screened human distances expected promote cooperativity. We find maximal spacing 26 nucleotides enriched naturally occurring compared control sequences. Furthermore, similar characteristics as indicated either co-expression within tissue or co-regulation disease context predicted target higher number cooperatively than unrelated miRNAs. These bioinformatic data were genome-wide sets biochemically validated targets derived Argonaute crosslinking immunoprecipitation (HITS-CLIP PAR-CLIP). To ease further research into combined function, developed miRco, database connecting respective involved distance-defined regulation (mips.helmholtz-muenchen.de/mirco). In conclusion, our findings suggest miRNA-target interaction widespread phenomenon may play an important role miRNA-mediated regulation.