Reorganization of mRNA-Protein Complexes during microRNA-Mediated Repression

Although microRNAs are thought to impact nearly every mammalian biological process, their molecular mechanism is not fully understood. Since all mRNAs are dressed with proteins to form mRNA-protein complexes (mRNPs), we reasoned that microRNAs might act by reorganizing target mRNPs. To test this hypothesis, we analyzed, on a transcriptome-wide scale, how the binding of core mRNP components (eIF4E, eIF4G, PABP and DDX6) was affected by mammalian microRNA-mediated repression. Despite the transient nature of the repression intermediates, we found that microRNAs stimulated the reorganization of target mRNPs. Furthermore, through analysis of poly(A)-tail length, we have been able to order the recruitment of DDX6 relative to deadenylation. These results suggest that modulation of core mRNP components represents a key node in posttranscriptional gene regulation.