MicroRNA-96 Directly Inhibits gamma-Globin Expression in Human Erythropoiesis
| LEADER | naa a22 4500 | ||
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| 001 | 528787047 | ||
| 005 | 20180924065502.0 | ||
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| 008 | 180924e20110728xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.3929/ethz-b-000038572 |2 doi |
| 024 | 7 | 0 | |a 10.1371/journal.pone.0022838 |2 doi |
| 035 | |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/38572 | ||
| 245 | 0 | 0 | |a MicroRNA-96 Directly Inhibits gamma-Globin Expression in Human Erythropoiesis |h [Elektronische Daten] |c [Imane Azzouzi, Hansjoerg Moest, Jeannine Winkler, Jean-Claude Fauchère, André P. Gerber, Bernd Wollscheid, Markus Stoffel, Markus Schmugge, Oliver Speer] |
| 246 | 0 | |a PLoS ONE | |
| 506 | |a Open access |2 ethresearch | ||
| 520 | 3 | |a Fetal hemoglobin, HbF (α2γ2), is the main hemoglobin synthesized up to birth, but it subsequently declines and adult hemoglobin, HbA (α2β2), becomes predominant. Several studies have indicated that expression of the HbF subunit γ-globin might be regulated post-transcriptionally. This could be confered by ∼22-nucleotide long microRNAs that associate with argonaute proteins to specifically target γ-globin mRNAs and inhibit protein expression. Indeed, applying immunopurifications, we found that γ-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 γ-globin expression by 50%, whereas the knock-down of endogenous microRNA-96 increased γ-globin expression by 20%. Moreover, luciferase reporter assays showed that microRNA-96 negatively regulates expression of γ-globin in HEK293 cells, which depends on a seedless but highly complementary target site located within the coding sequence of γ-globin. Based on these results we conclude that microRNA-96 directly suppresses γ-globin expression and thus contributes to HbF regulation. | |
| 540 | |a Creative Commons Attribution 3.0 Unported |u http://creativecommons.org/licenses/by/3.0 |2 ethresearch | ||
| 700 | 1 | |a Azzouzi |D Imane |e joint author | |
| 700 | 1 | |a Moest |D Hansjoerg |e joint author | |
| 700 | 1 | |a Winkler |D Jeannine |e joint author | |
| 700 | 1 | |a Fauchère |D Jean-Claude |e joint author | |
| 700 | 1 | |a Gerber |D André P. |e joint author | |
| 700 | 1 | |a Wollscheid |D Bernd |e joint author | |
| 700 | 1 | |a Stoffel |D Markus |e joint author | |
| 700 | 1 | |a Schmugge |D Markus |e joint author | |
| 700 | 1 | |a Speer |D Oliver |e joint author | |
| 773 | 0 | |t PLoS ONE |d Lawrence, KS, USA : Public Library of Science |g 6 (7), p. e22838 |x 1932-6203 | |
| 856 | 4 | 0 | |u http://hdl.handle.net/20.500.11850/38572 |q text/html |z WWW-Backlink auf das Repository (Open access) |
| 908 | |D 1 |a Journal Article |2 ethresearch | ||
| 950 | |B ETHRESEARCH |P 856 |E 40 |u http://hdl.handle.net/20.500.11850/38572 |q text/html |z WWW-Backlink auf das Repository (Open access) | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Azzouzi |D Imane |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Moest |D Hansjoerg |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Winkler |D Jeannine |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Fauchère |D Jean-Claude |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Gerber |D André P. |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Wollscheid |D Bernd |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Stoffel |D Markus |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Schmugge |D Markus |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Speer |D Oliver |e joint author | ||
| 950 | |B ETHRESEARCH |P 773 |E 0- |t PLoS ONE |d Lawrence, KS, USA : Public Library of Science |g 6 (7), p. e22838 |x 1932-6203 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B ETHRESEARCH |F ETHRESEARCH |b ETHRESEARCH |j Journal Article |c Open access | ||