Intrinsic disorder of a nucleoplasmin ‐like histone chaperone specifies its discrete nuclear and nucleolar functions

All nucleoplasmin (NPM) proteins have large regions of intrinsic disorder, but It is not clear if intrinsic disorder is an absolute requirement for all functions attributed to NPMs. We show that disordered regions of a yeast NPM-like protein, and lysine polyphosphorylation sites within them, are dispensable for NPM nucleolar functions, but key to NPM-mediated gene repression in the nucleus. Nucleoplasmin (NPM) histone chaperones regulate distinct processes in the nucleus and nucleolus. While intrinsically disordered regions (IDRs) are hallmarks of NPMs, it is not clear if all NPM functions require these unstructured features. We assessed the importance of IDRs in a yeast NPM-like protein and found that regulation of rDNA copy number and genetic interactions with the nucleolar RNA surveillance machinery require the highly conserved FKBP prolyl isomerase domain, but not the NPM domain or IDRs. By contrast, transcriptional repression in the nucleus requires IDRs. Furthermore, multiple lysines in poly-acidic serine/lysine motifs of IDRs are required for both lysine polyphosphorylation and NPM-mediated transcriptional repression. These results demonstrate that this NPM-like protein relies on IDRs only for some of its chromatin-related functions.
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Research Letter Source Type: research