The Darnell paper, Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps, published in the most recent issue of nature seems to be widely read by most people who care about RNA and or bioinformatics. This paper is important because Darnell, via high throughput sequencing of RNAs isolated by crosslinking immunoprecipitation, is able to differentiate between targets that are found by scanning the genome for the 6-8nt sequence complementary to the conserved "seed" sequence of an miRNA from those that show functional protein-RNA interaction.
Most bioinformatic approaches used to predict miRNA targets restrict their search to conserved target sites in the 3'UTR, the HITS-CLIP method, on the other hand, was able to find target sites that mapped to coding sequences, interenic regions, and non-coding RNAs. After identifying targets of miRNA, Darnell and his group wanted to see if the Ag0-mRNA/ Ago-miRNA interactions resulted in downregulation of the target mRNA. In order to determine this, HeLa cells were transfected with brain-specific miRNA (mir-124) and then used HITS-CLIP to determinte ago-mRNA clusters. According to the results, mRNA's that were bound by mir-124 were noticeably down regulated once transfected at the protein and mRNA level.
...Beyond the paper, i think it is interesting although not surprising that the HITS-CLIP method found targets in non-coding RNAs. In my opinion (which at this point probably isn't worth much given i have very limited experience with miRNA) might mean that these regulatory bits of RNA (miRNA) regulate other regulatory elements which in turn regulate the robustness of an even greater regulatory system. The Darnell paper restricted most (or all) of their analysis to conserved miRNA targets, however, I think that exploring the relationship between miRNAs and other non-coding RNA could offer insight into the feedback loops that govern how our genes are expressed.
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