  Recent experimental results on the effect of miRNA on the decay of its target
mRNA have been analyzed against a previously hypothesized single molecule
degradation pathway. According to that hypothesis, the silencing complex
(miRISC) first interacts with its target mRNA and then recruits the protein
complexes associated with NOT1 and PAN3 to trigger deadenylation (and
subsequent degradation) of the target mRNA. Our analysis of the experimental
decay patterns allowed us to refine the structure of the degradation pathways
at the single molecule level. Surprisingly, we found that if the previously
hypothesized network was correct, only about 7% of the target mRNA would be
regulated by the miRNA mechanism, which is inconsistent with the available
knowledge. Based on systematic data analysis, we propose the alternative
hypothesis that NOT1 interacts with miRISC before binding to the target mRNA.
Moreover, we show that when miRISC binds alone to the target mRNA, the mRNA is
degraded more slowly, probably through a deadenylation-independent pathway. The
new biochemical pathway we propose both fits the data and paves the way for new
experimental work to identify new interactions.
