Electronegative clusters modulate folding status and RNA binding of unstructured RNA‐binding proteins

Abstract Electronegative clusters (ENCs) made up of acidic residues and/or phosphorylation sites are the most abundant repetitive sequences in RNA‐binding proteins. Previous studies have indicated that ENCs inhibit RNA binding for structured RNA‐binding domains (RBDs). However, this is not the case for the unstructured RBD in histone pre‐mRNA stem‐loop binding protein (SLBP). The SLBP RBD contains 70 amino acids and is followed by a phosphorylatable ENC. ENC phosphorylation increases RNA‐binding affinity of SLBP to the sub‐picomolar range. In this study,