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Free keywords:
Open Access; miRNA; mRNA complex degradation; mRNA decay; stochastic modeling; single molecule; open access
Abstract:
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 proposed
here both fits the data and paves the way for new experimental work to identify new interactions.
