HuR thermal stability is dependent on domain binding and upon phosphorylation.
Human antigen R (HuR) is a multitasking RNA binding protein involved in posttranscriptional regulation by recognizing adenine- and uracile-rich elements placed at the 3'-untranslated regions of messenger RNAs (mRNAs). The modular architecture of the protein, which consists of two N-terminal RNA recognition motifs (RRMs) in tandem spaced from a third one by a nuclear-cytoplasmic shuttling sequence, controls the stability of many mRNA targets, as well as their translation rates. A higher level of regulation comes from the fact that both localization and function of HuR are strictly regulated by phosphorylation. Here, we report how the thermal stability of RRM2 is decreased by the presence of RRM1, indicating that both domains are interacting in solution. In addition, even though no significant structural changes are observed among mutants of HuR RRM12 mimicking phosphorylated species, slight differences in stability are appreciable, which may explain the RNA binding activity of HuR.
Instituto de Bioquímica Vegetal y Fotosíntesis, cicCartuja, Universidad de Sevilla-CSIC, Sevilla, Spain.
Rafael Manfred
RM
Scheiba
Angeles
A
Aroca
Irene
I
Díaz-Moreno
D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D051959:ELAV Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D013696:Temperature
D020413:3' Untranslated Regions; D051959:ELAV Proteins