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 Blood, 15 February 2005, Vol. 105, No. 4, pp. 1807-1809.
Prepublished online as a Blood First Edition Paper on October 12, 2004; DOI 10.1182/blood-2004-02-0454.

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Submitted February 5, 2004
Accepted October 5, 2004

Butyrate increases the efficiency of translation of {gamma}-Globin mRNA

Rona S Weinberg*, Xijun Ji, Millicent Sutton, Susan Perrine, Yelena Galperin, Qiliang Li, Stephen A Liebhaber, George Stamatoyannopoulos, and George F Atweh

Department of Medicine, Division of Hematology/Oncology, Mount Sinai School of Medicine, New York, NY, USA
Departments of Genetics and Medicine, University of Pennsylvania, Philadelphia, PA, USA
Hemoglobinopathy Thalassemia Research Unit, Boston University School of Medicine, Boston, MA, USA
Division of Medical Genetics, University of Washington, Seattle, WA, USA

* Corresponding author; email: rweinberg{at}nybloodcenter.org.

Fetal hemoglobin (Hb F) levels increase in the majority of sickle cell patients 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 {gamma}-globin chain synthesis markedly increased within 24 hours of butyrate exposure, without concomitant changes in reticulocyte {gamma}-globin mRNA levels. This suggests that butyrate might induce Hb F by increasing the efficiency of translation of {gamma}-globin mRNA. This hypothesis was confirmed by ribosome loading studies that demonstrated enrichment of the polysomal fraction of reticulocytes with {gamma}-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 {gamma}-globin genes.


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