RNA in polysomes is an inhibitor of manganese superoxide dismutase RNA-binding protein activity.

Abstract

A redox-sensitive protein in rat lung binds to the 3'-untranslated region (3'-UTR) of manganese superoxide dismutase (Mn-SOD) mRNA; the activity of this Mn-SOD RNA-binding protein (Mn-SOD-BP) is greater in 12,000-g supernatant fractions (S12) from neonates than in S12 from adults (H. Fazzone, A. Wangner, and L. B. Clerch. J. Clin. Invest. 92: 1278-1281, 1993). To determine the mechanism underlying this developmental difference, lung subcellular fractions were tested for their effect on Mn-SOD-BP activity. Protein in the 130,000-g supernatant (S130) of lung extracts bound the 3'-UTR. However, the developmental difference in binding was not present in S130. The 130,000-g pellet (P130) did not bind the 3'-UTR; rather, it contained an inhibitor of Mn-SOD-BP activity. Addition of P130 to S130 decreased RNA binding in a dose-dependent manner. Furthermore, adult P130 was a more potent inhibitor of RNA-binding activity than neonatal P130. These data indicate that the developmental difference in Mn-SOD-BP activity is due, in part, to an inhibitor in P130. Biochemical characterization revealed that the inhibitor is an RNA that may participate in the posttranscriptional control of Mn-SOD gene expression.