Dynamic changes in RNA–protein interactions and RNA secondary structure in mammalian erythropoiesis

Abstract

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 throughout the process and determine a set of corresponding protein-bound sequence motifs along with 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.

The HNRNPF/H RNA binding proteins and disease

“…In contrast, homozygous disruption of Hnrnph1 on a C57BL/6N background results in preweaning lethality, whereas heterozygous mice exhibit disruption of erythropoiesis. Of note, a recent study by Shan et al highlighted this latter observation as part of their analysis of the differential binding of RBPs, including HNRNPF/H proteins, to RNAs that exhibit changes in expression during red blood cell differentiation (Shan et al, 2021). Generation of another line of Hnrnph1 knockout mice resulted in no post‐13.5‐week embryos, though its conditional deletion in germline cells produced viable offspring (Feng et al, 2022).…”

Recent advances in RNA structurome

“…Protein interaction profiling sequencing (PIP-seq) complements PARS-seq by including an additional step in which RNAs and proteins are cross-linked via formaldehyde or UV light prior to enzymatic probing, providing extra information about RNA-protein interactions (Gosai et al, 2015). This method was initially developed in the Arabidopsis nucleus, which is also applicable to the mammalian species (Shan et al, 2021;Silverman et al, 2014). A DMSbased in vivo RNA structure profiling method was simultaneously established in yeast and Arabidopsis (Ding et al, 2015;Ding et al, 2014;Rouskin et al, 2014).…”