Iron-sensitive RNA regulation by poly C binding proteins

Iron is essential for normal cellular function. Homeostatic responses to low iron availability have long been known to rely on posttranscriptional mechanisms. Poly C binding proteins (PCBPs) are essential RNA binding proteins that regulate alternative splicing, translation and RNA stability. They also serve as critical iron chaperones that manage intracellular iron flux. However, the impact of cellular iron levels on the PCBP-directed transcriptome has not been globally evaluated. We have found broad transcriptome changes in response to low iron availability consistent with numerous operant posttranscriptional mechanisms that sense iron. By comparing gene expression and alternative splicing directed by PCBPs to the iron-sensitive transcriptome, we found genes with iron-sensitive PCBP RNA regulation. Further, we demonstrate that cellular iron levels impact PCBP1 RNA binding. Our data show a large-scale RNA regulatory response to cellular iron levels and open the possibility for other iron-sensitive RNA binding proteins.