5-Fluorouracil RNA incorporation

5-Fluorouracil RNA incorporation describes the biochemical mechanism by which the antimetabolite 5-fluorouracil (5-FU) exerts cytotoxicity by substituting for uracil in cellular RNA species. After administration, 5-FU is converted through a series of enzymatic steps into 5-fluorouridine triphosphate (FUTP), which competes with the endogenous nucleotide uridine triphosphate (UTP) for incorporation into nascent RNA strands by RNA polymerases (Grem, 2000, PubMed: 11033135). This incorporation affects multiple classes of RNA, including ribosomal RNA (rRNA), messenger RNA (mRNA), and small nuclear RNA (snRNA), leading to defects in RNA splicing, polyadenylation, and ribosome biogenesis (Longley et al., 2003, PubMed: 12778139). These disruptions ultimately impair protein synthesis and trigger cell cycle arrest or apoptosis in malignant cells. While 5-FU is also well-known for inhibiting DNA synthesis via thymidylate synthase, the RNA-directed effects are considered a primary driver of its clinical efficacy and side effect profile in treating solid tumors such as colorectal and breast cancers (Zhang et al., 2008, PubMed: 18457614).

Other names

RNA-directed 5-fluorouracil toxicity5-FU RNA incorporationFUTP incorporation into RNA5-fluorouridine triphosphate RNA incorporation

The drug 5-fluorouracil is metabolically activated to 5-fluorouridine triphosphate (FUTP), which competes with uridine triphosphate (UTP) for incorporation into RNA, thereby disrupting RNA processing, splicing, and translation (Longley et al., 2003, PubMed: 12778139).