Alternative transcription and splicing of the human porphobilinogen deaminase gene result either in tissue-specific or in housekeeping expression.

TLDR

Porphobilinogen deaminase is a cytosolic enzyme of the heme biosynthetic pathway that exists as two isoforms encoded by distinct mRNAs, one ubiquitous and one erythroid‑specific. The authors show that these two mRNAs arise from two overlapping transcription units. Cloning and characterization of the single human PBGD gene, comprising 15 exons over 10 kb, revealed a ubiquitous promoter with housekeeping features and a downstream erythroid‑specific promoter homologous to beta‑globin promoters.

Abstract

Porphobilinogen deaminase [PBGD; porphobilinogen ammonia-lyase (polymerizing), EC 4.3.1.8] is a cytosolic enzyme involved in the heme biosynthetic pathway. Two isoforms of PBGD, encoded by two mRNAs differing solely in their 5' end, are known: one is found in all cells and the other is present only in erythroid cells. We have previously shown that the human PBGD is encoded by a single gene and have now cloned and characterized this gene, which is split into 15 exons spread over 10 kilobases of DNA. We demonstrate that the two mRNAs arise from two overlapping transcription units. The first one (upstream) is active in all tissues and its promoter has some of the structural features of a housekeeping promoter; the second, located 3 kilobases downstream, is active only in erythroid cells and its promoter displays structural homologies with the beta-globin gene promoters.