microRNA Targeting mRNAs: More Exceptions Than Rules

from Epigenie blog – May 5, 2010 

Up to now, all miRNAs have been assumed to work the same way when it comes to finding their mRNA targets, but a new paper shows that miRNAs behave more like rugged individualists in how they function.

Researchers from the University of Kentucky broke out the RIP-Chip method (Argonaute, aka AGO, co-IP assays coupled with downstream microarray analysis) in H4 glioneuronal cells transfected with certain miRNAs to get an idea of what each miRNA is targeting and how. The RIP-Chip technique showed hard evidence of what mRNAs are targeted, and even the proteins involved in the microribonucleoparticles (miRNPs) for each miRNA tested (miR-107, miR-124, miR-128, and miR-320). After looking over targets of each miRNA, here’s what they found:

  • miR-124 displayed a standard targeting profile: using a 5’ seed sequence to target a 3’ mRNA UTR.
  • miR-107, however, targeted the open reading frame (ORF) regions, and not the 3’UTRs, of its targets.
  • miR-128 and miR-320 were shown to utilize more of a mixture of 5’ and 3’ seed regions to bind targets.

Sure, the authors only looked at one cell-line, and RIP-Chip assays can only asses non-degraded targets, but the take-home message is the same: miRNAs are like snowflakes, every one is unique. So, the only way to really know what your favorite miRNA is targeting, is to go test it out.

Get zeroed in on all the miRNA targeting details in RNA Biology, May 2010.

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