Beyond intermediary metabolism: characterization of the moonlighting nucleic acid binding function of human serine hydroxymethyltransferase

The present thesis aims to dissect the moonlighting nucleic acid binding activity of human cytosolic serine hydroxymethyltransferase (SHMT1), a double-faced metabolic enzyme. Indeed, the work characterizes the interaction between SHMT1 and RNA molecules in vitro as well as in cell models, thus unraveling an unexpected complex mechanism in which the synergy among SHMT1, RNA and metabolites fine tunes the compartmentalization of serine metabolism in lung cancer cells. On the other hand, the study of the SHMT1-DNA complexes, presented herein, set the basis to hypothesize a nuclear function of the enzyme mediated by its binding with the DNA. Overall this manuscript is pioneer in characterizing the moonlighting nucleic acid binding activity of SHMT1 and, most of all, in determining the functional relevance of such phenomenon, thus placing SHMT1 in the network which interconnects intermediary metabolism with gene replication and gene expression.