If your boss were to tell you that you’re acting like a real ass, you’d probably start packing your desk, unless you’re auditioning for Eeyore in that upcoming Winnie the Pooh play in which case you’d be stoked. So much in life is all about the context…and miRNA regulation is no exception. A recent report from scientists at the Beckman Research Institute of the City of Hope in California shows that when it comes to miRNA-target interactions, the sequence context surrounding miRNA target sites are also a big factor in miRNA effectiveness.
Noting the current difficulty in miRNA target prediction, the team from City of Hope set out to find some nuggets of wisdom to help the issue. The first step was to confirm that their model gene, RhoB was in fact a true target of miR-223. Once that was validated, the group set out experimenting with the two miR-223 target sites in RhoB’s 3’UTR, and the surrounding sequence. Their work revealed some interesting tidbits about miRNA function:
- Different miRNA target sites function at different strengths
- Target sites are influenced by surrounding sequences
- AU-rich sequence elements enhance miRNA function for downstream target sites, not upstream.
- Translational repressors like Tristetraprolin (TPP) and cytoplasmic polyadenylation element binding protein (CPEB) motifs enhance miRNA knockdown
They went on to show that these results were not specific to just miR-223, and demonstrated the importance of looking at the entire, full length 3’ UTR in these types of studies.
So, you can add sequence context to the list of things to check for on your next search for your favorite miRNA target gene.
To double-check that nothing here was taken out of context, check out the paper at Nucleic Acids Research, October 2009.