The gene regulation of mRNA degradation mediated by elements rich in adenine and uracil bases (ARE) is important both in cellular and physiological proliferation in the immune response and cardiovascular tone.

One of the ARE binding proteins is the KSRP (K homology Splicing Regulator-Protein) that recruits the exosome favoring different mRNA degradation. By using techniques of nuclear magnetic resonance (NMR) and biophysical tools such as circular dichroism (CD) and techniques of calorimetry (ITC) in the study by Dr. Diaz-Moreno, Institute of Plant Biochemistry and Photosynthesis Sevilla (US-CSIC), shows that the KSRP protein activity is regulated by phosphorylation of serine residue 193 of the N-terminus of one of its domains (KH1 RNA-binding). Specifically, inside the cell, the phosphorylation involves interaction between KSRP and nuclear protein 14-3-3C, a ubiquitous regulatory protein that binds to phosphorylated protein polypeptide chains reducing the ability of KSRP to interact and degrade their mRNA targets.

At the molecular level KH1 phosphorylation leads the full unfolding of that domain (structurally unstable and atypical), causing a new binding site for 14-3-3Ç. At this site 14-3-3C is capable of discriminating between the two forms of the KH1 domain (phosphorylated and non phosphorylated) by encouraging the nuclear localization of KSRP.
These works demonstrate the high level of integration complexity of the routes of RNA metabolism and signaling pathways.