First epigenetics knocked Mendel off the high horse of simple inheritance and now it’s taking a shot at Watson and Crick. It seems that not even base-pairing is safe these days, with microRNA targeting demonstrating that it is anything but simple. In its latest political statement this member of the non-coding party has been caught exerting its influence in some new territory via non-Watson-Crick base pairing in the miRNA seed region.
Isidore Rigoutsos and a team from Thomas Jefferson University (Philadelphia) continued their mission to tease apart the mechanisms of miRNA target prediction, by adding new insights to miRNAs targeting preferences, like in their earlier work on mammalian 5′ UTR miRNA targeting. But now they’ve caught some other “non-canonical” business going down, here’s some of the insights:
- miRNAs change things up both architecturally (i.e. bulge vs. contiguous pair) and at the sequence (Watson-Crick vs. G:U pairs) level.
- There are some interesting patterns in miRNA targeting behavior across cell types. “For some cell types intergenic and intronic targets were more frequent whereas in other cell types mRNA targets prevailed.”
- There’s also a surprising pattern in the distribution of the number of targets that individual miRNAs have.
- While the Argonaute loaded miRNA profiles were consistent across biological replicates, their targets were much more varied and dynamic nature across the replicates.
The authors propose that the low relative abundance of standard model targets doesn’t hold up to the new expanded models that view the whole mRNA as fair game.
Rigoustos shares that “Our study shows that even conserved miRNAs that we share with animals and insects can have very different behavior across organisms and even across different tissues in our bodies. If the repertoire of targets for one miRNA can be so different between cells of the same organism it is likely to also be different from one organism to the other. The findings may help explain why the microRNA field has run into difficulty when translating these powerful molecules into therapies for diseases ranging from cancer to diabetes. There is still so much we don’t know about how miRNAs work in the body.”
Expand your targeting horizons in Nature’s Scientific Reports, August 2014