Butyrate increases the efficiency of translation of γ-globin mRNA

Abstract

Fetal hemoglobin (Hb F) levels increase in most patients with sickle cell disease following intermittent butyrate therapy. Although the full effects of butyrate on Hb F levels usually require multiple treatment cycles, in some patients a peak level is achieved after a few days of butyrate therapy. Our investigation of the mechanism(s) responsible for this rapid induction of Hb F by butyrate showed that reticulocyte γ-globin chain synthesis markedly increased within 24 hours of butyrate exposure, without concomitant changes in reticulocyte γ-globin mRNA levels. This suggests that butyrate might induce Hb F by increasing the efficiency of translation of γ-globin mRNA. This hypothesis was confirmed by ribosome loading studies that demonstrated enrichment of the polysomal fraction of reticulocytes with γ-globin mRNA following butyrate exposure. Thus, the induction of Hb F by butyrate may be mediated by translational effects in addition to its well-known effects on transcription of the γ-globin genes. © 2005 by The American Society of Hematology.