Microrna-96 directly inhibits γ-Globin expression in human erythropoiesis
Azzouzi, I, Moest, H, Winkler, J, Fauchère, J-C, Gerber, AP, Wollscheid, B, Stoffel, M, Schmugge, M and Speer, O (2011) Microrna-96 directly inhibits γ-Globin expression in human erythropoiesis PLoS ONE, 6 (7).
Azzouzi et al. 2011 PLoS ONE.pdf
Available under License : See the attached licence file.
Fetal hemoglobin, HbF (a2c2), is the main hemoglobin synthesized up to birth, but it subsequently declines and adult hemoglobin, HbA (a2b2), becomes predominant. Several studies have indicated that expression of the HbF subunit c-globin might be regulated post-transcriptionally. This could be confered by ,22-nucleotide long microRNAs that associate with argonaute proteins to specifically target c-globin mRNAs and inhibit protein expression. Indeed, applying immunopurifications, we found that c-globin mRNA was associated with argonaute 2 isolated from reticulocytes that contain low levels of HbF (,1%), whereas association was significantly lower in reticulocytes with high levels of HbF (90%). Comparing microRNA expression in reticulocytes from cord blood and adult blood, we identified several miRNAs that were preferentially expressed in adults, among them miRNA-96. The overexpression of microRNA-96 in human ex vivo erythropoiesis decreased c-globin expression by 50%, whereas the knock-down of endogenous microRNA-96 increased c-globin expression by 20%. Moreover, luciferase reporter assays showed that microRNA-96 negatively regulates expression of c-globin in HEK293 cells, which depends on a seedless but highly complementary target site located within the coding sequence of c-globin. Based on these results we conclude that microRNA-96 directly suppresses c-globin expression and thus contributes to HbF regulation.
|Divisions :||Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Microbial and Cellular Sciences|
|Identification Number :||10.1371/journal.pone.0022838|
|Additional Information :||Copyright 2011 Azzouzi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
|Depositing User :||Symplectic Elements|
|Date Deposited :||14 Mar 2012 17:19|
|Last Modified :||23 Sep 2013 19:13|
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