Figure 3.

5-Fluorouracil inhibits ribonucleic acid pseudouridylation including the conversion of uridine to pseudouridine and formation of stable ribonucleoprotein complexes. These actions will interrupt cellular tRNA, pre-mRNA and rRNA production and also post-transcriptional modification, leading to RNA biosynthesis cessation. Moreover, 5-fluorouracil (5-FU) disrupts the assembly and activity of snRNA and protein complexes through its effect on the pseudouridylation of U2 snRNA, thereby inhibiting the splicing of pre-mRNA[21]. Because of the similarity between the 5-FU metabolite fluorouridine triphosphate (FUTP) with uridine triphosphate, FUTP can be identified by RNA polymerases and incorporated into both nuclear and cytoplasmic RNA molecules, interrupting normal RNA processing and function[22]. RNA-based 5-FU toxicity decreases the cellular levels of the nuclear exosome Rrp6 or exosome component 10, a breakdown complex for RNA, banning the effectual turn-over of aberrant RNA transcripts[21]. FUMP: Fluorouridine monophosphate; FUDP: Fluorouridine diphosphate.