1. Combinatorial mRNA binding by AUF1 and Argonaute 2 controls decay of selected target mRNAs.
- Author
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Wu X, Chesoni S, Rondeau G, Tempesta C, Patel R, Charles S, Daginawala N, Zucconi BE, Kishor A, Xu G, Shi Y, Li ML, Irizarry-Barreto P, Welsh J, Wilson GM, and Brewer G
- Subjects
- 3' Untranslated Regions, HeLa Cells, Heterogeneous Nuclear Ribonucleoprotein D0, Humans, K562 Cells, Argonaute Proteins metabolism, Heterogeneous-Nuclear Ribonucleoprotein D metabolism, RNA Stability, RNA, Messenger metabolism
- Abstract
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 (AGO2), which is an essential effector of microRNA-induced gene silencing. Depending on the specific mRNA examined, AUF1 and AGO2 binding is proportional/cooperative, reciprocal/competitive or independent. For most mRNAs in which AUF1 affects their decay rates, mRNA degradation requires AGO2. Thus, AUF1 and AGO2 present mRNA-specific allosteric binding relationships for co-regulation of mRNA degradation.
- Published
- 2013
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