New Research Shows How N-Terminal Acetylation Shapes Individual Protein Fate

Using genome-wide CRISPR knockout screens combined with cellular phenotyping, researchers from the University of Bergen determined how N-terminal acetylation protects proteins from degradation in human cells.

According to Thomas Arnesen, senior author of the paper published in Nature Communications, N-terminal acetylation is one of the most common protein modifications in human cells, but despite being everywhere in human cells, the functional role of this modification remains mysterious.

First author Sylvia Varland focused her research on one of the major human NAT enzymes, NatC, and the genome-wide screening of human NatC KO cells revealed many human genes likely to be involved in the function of N-terminal acetylation.

Subsequently, the team explored the molecular implications of her genetic findings. Biochemical, cell biology and proteomics experiments demonstrated that N-terminal acetylation acts as shield to protect many proteins from protein degradation. Proteins lacking N-terminal acetylation were recognized by the cellular degradation machinery.

“This work untangles some of the secrets and shows how N-terminal acetylation shape individual protein fate”, Arnesen concluded.