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Folate-mediated one-carbon metabolism is a network of interdependent pathways in which single carbon units derived from serine or glycine are activated and used for the biosynthesis of purines, thymidylate, and methionine. Folate-mediated one-carbon metabolism plays essential roles in development, DNA replication, the maintenance of genome stability, and gene expression. Consequently, impairments in this network are associated with an increased incidence of neural tube defects, cardiovascular disease, and cancer. Cytoplasmic serine hydroxymethyltransferase (cSHMT) serves as a source of folate-activated one-carbon units by catalyzing the conversion of serine and tetrahydrofolate (THF) to glycine and 5,10-methyleneTHF, the one-carbon donor in the thymidylate biosynthesis reaction. cSHMT is regulated by several factors at both the transcriptional and translational levels. At the translational level, cSHMT expression is enhanced through an internal ribosome entry site (IRES) located in the 5’untranslated region (UTR) of the transcript. IRESes are cis-acting regulatory elements that permit 5’-cap-independen