Global Analysis of the RNA-Protein Interaction and RNA Secondary Structure Landscapes Identifies Dynamic Changes During Mammalian Erythropoiesis (mRNA)

Two features of eukaryotic RNA molecules that regulate their post-transcriptional fates are RNA secondary structure and RNA-binding protein (RBP) interaction sites. However, a comprehensive global overview of the dynamic nature of these sequence features during erythropoiesis has never been obtained. Here, we use our ribonuclease-mediated structure and RBP-binding site mapping approach to reveal the global landscape of RNA secondary structure and RBP-RNA interaction sites and the dynamics of these features during this important developmental process. We identify dynamic patterns of RNA secondary structure and RBP binding that are consistently anti-correlated throughout mRNAs during erythropoiesis. Additionally, we determine a set of protein-bound sequence motifs and their dynamic structural and RBP binding contexts. Finally, using these dynamically bound sequences, we identify a number of RBPs that have known and putative key functions in post-transcriptional regulation during mammalian erythropoiesis. In total, this global analysis reveals new post-transcriptional regulators of mammalian blood cell development. mRNA-seq of 2 biological replicates of MEL cells at day 0, day 2, and day 4 post differentiation induction by DMSO