Combinatorial mRNA binding by AUF1 and Argonaute 2 controls decay of selected target mRNAs

摘要

The RNA-binding protein AUF1 binds AU-rich elements in 3-untranslated regions to regulate mRNA degradation and/or translation. Many of these mRNAs are predicted microRNA targets as well. An emerging theme in post-transcriptional control of gene expression is that RNA-binding proteins and microRNAs co-regulate mRNAs. Recent experiments and bioinformatic analyses suggest this type of co-regulation may be widespread across the transcriptome. Here, we identified mRNA targets of AUF1 from a complex pool of cellular mRNAs and examined a subset of these mRNAs to explore the links between RNA binding and mRNA degradation for both AUF1 and Argonaute 2 (AG02), which is an essential effector of microRNA-induced gene silencing. Depending on the specific mRNA examined, AUF1 and AG02 binding is proportional/cooperative, reciprocal/competitive or independent. For most mRNAs in which AUF1 affects their decay rates, mRNA degradation requires AG02. Thus, AUF1 and AG02 present mRNA-specific allosteric binding relationships for co-regulation of mRNA degradation.