The basis for the intestine-specific expression of apoprotein B-48 is RNA editing. In mammals, the gene encoding apolipoprotein B (ApoB) produces two main isoforms: ApoB-100 and ApoB-48. These isoforms result from a single gene through a process called RNA editing, specifically in the intestine. Here's how this process works:
- ApoB mRNA undergoes a post-transcriptional modification in the intestine where a specific cytidine residue (C) is deaminated to uridine (U).
- This editing occurs at nucleotide 6666, which introduces a premature stop codon (UAA) within the mRNA.
- Due to this premature stop codon, the translation of ApoB mRNA in the intestine produces a truncated protein, ApoB-48, which is shorter than ApoB-100.
- In contrast, liver cells do not undergo this RNA editing process, allowing for the full-length translation of ApoB-100.
RNA editing is, therefore, the critical mechanism distinguishing ApoB-48 from ApoB-100 and ensuring its specific expression in intestinal tissues.