IDENTIFICATION OF A HIGHLY CONSERVED 3' UTR IN THE TRANSLATIONALLY REGULATED MESSENGER-RNA FOR PROSTAGLANDIN SYNTHASE

Prostaglandin H synthase (E.C. 1.14.99.1) is induced by growth factors and lymphokines such as EGF and IL-1, and is suppressed by anti-inflammatory glucocorticoids. Inhibition of enzyme synthesis by glucocorticoids is mediated by a novel translational control that appears to involve conversion of the PG synthase mRNA into a cryptic non-hybridizable form. In order to understand expression of the enzyme in more detail, a full length 2.8 Kb cDNA was cloned from a human embryonic lung cell cDNA library and the complete mRNA including the 3' untranslated region (3' UTR), was sequenced. The coding sequence for the human PG synthase shows greater than 90% homology with the sheep and mouse enzymes. A high degree of conservation (70%), however, was also observed in the approximately 750 nucleotide sequence that comprises the 3' non-coding domain of both sheep and human PG synthase mRna's and with the approximately 900 nucleotide 3' UTR of the mouse RNA (68% sheep vs mouse; 47% human vs mouse). Extensive microregions of 10-30 nucleotides are distributed throughout the 3' UTR where homology between species in 95-100%. This high degree of conservation in a non-coding region and recent evidence from other genes suggests that these 3' UTR sequences have important regulatory functions possibly related to translational control of this mRNA by growth factors and glucocorticoids.