MiR-328 Functions As an RNA Decoy to Modulate HnRNP E2 Regulation of MRNA Translation in Leukemic Blasts

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2010 Mar 10

PMID 20211135

Citations 267

Authors

Anna M Eiring

Jason G Harb

Paolo Neviani

Christopher Garton

Joshua J Oaks

Riccardo Spizzo

Shujun Liu

Sebastian Schwind

Ramasamy Santhanam

Christopher J Hickey

Heiko Becker

Jason C Chandler

Raul Andino

Jorge Cortes

Peter Hokland

Claudia S Huettner

Ravi Bhatia

Denis C Roy

Stephen A Liebhaber

Michael A Caligiuri

Guido Marcucci

Ramiro Garzon

Carlo M Croce

George A Calin

Danilo Perrotti

Affiliations

Soon will be listed here.

Abstract

MicroRNAs and heterogeneous ribonucleoproteins (hnRNPs) are posttranscriptional gene regulators that bind mRNA in a sequence-specific manner. Here, we report that loss of miR-328 occurs in blast crisis chronic myelogenous leukemia (CML-BC) in a BCR/ABL dose- and kinase-dependent manner through the MAPK-hnRNP E2 pathway. Restoration of miR-328 expression rescues differentiation and impairs survival of leukemic blasts by simultaneously interacting with the translational regulator poly(rC)-binding protein hnRNP E2 and with the mRNA encoding the survival factor PIM1, respectively. The interaction with hnRNP E2 is independent of the microRNA's seed sequence and it leads to release of CEBPA mRNA from hnRNP E2-mediated translational inhibition. Altogether, these data reveal the dual ability of a microRNA to control cell fate both through base pairing with mRNA targets and through a decoy activity that interferes with the function of regulatory proteins.

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References

Chang J, Santhanam R, Trotta R, Neviani P, Eiring A, Briercheck E . High levels of the BCR/ABL oncoprotein are required for the MAPK-hnRNP-E2 dependent suppression of C/EBPalpha-driven myeloid differentiation. Blood. 2007; 110(3):994-1003. PMC: 1924762. DOI: 10.1182/blood-2007-03-078303. View

Guil S, Caceres J . The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a. Nat Struct Mol Biol. 2007; 14(7):591-6. DOI: 10.1038/nsmb1250. View

Eiring A, Neviani P, Santhanam R, Oaks J, Chang J, Notari M . Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis. Blood. 2007; 111(2):816-28. PMC: 2200861. DOI: 10.1182/blood-2007-05-090472. View

Fujimura K, Kano F, Murata M . Identification of PCBP2, a facilitator of IRES-mediated translation, as a novel constituent of stress granules and processing bodies. RNA. 2008; 14(3):425-31. PMC: 2248264. DOI: 10.1261/rna.780708. View

Johnnidis J, Harris M, Wheeler R, Stehling-Sun S, Lam M, Kirak O . Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature. 2008; 451(7182):1125-9. DOI: 10.1038/nature06607. View

Glisovic T, Bachorik J, Yong J, Dreyfuss G . RNA-binding proteins and post-transcriptional gene regulation. FEBS Lett. 2008; 582(14):1977-86. PMC: 2858862. DOI: 10.1016/j.febslet.2008.03.004. View

Bueno M, Perez de Castro I, Gomez de Cedron M, Santos J, Calin G, Cigudosa J . Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell. 2008; 13(6):496-506. DOI: 10.1016/j.ccr.2008.04.018. View

Wang C, Lee D, Deng Z, Jeyapalan Z, Lee S, Kahai S . MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression. PLoS One. 2008; 3(6):e2420. PMC: 2409976. DOI: 10.1371/journal.pone.0002420. View

Hinman M, Lou H . Diverse molecular functions of Hu proteins. Cell Mol Life Sci. 2008; 65(20):3168-81. PMC: 2580827. DOI: 10.1007/s00018-008-8252-6. View

10.

Agirre X, Jimenez-Velasco A, Jose-Eneriz E, Garate L, Bandres E, Cordeu L . Down-regulation of hsa-miR-10a in chronic myeloid leukemia CD34+ cells increases USF2-mediated cell growth. Mol Cancer Res. 2008; 6(12):1830-40. DOI: 10.1158/1541-7786.MCR-08-0167. View

11.

Friedman R, Farh K, Burge C, Bartel D . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2008; 19(1):92-105. PMC: 2612969. DOI: 10.1101/gr.082701.108. View

12.

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

13.

Vasudevan S, Tong Y, Steitz J . Switching from repression to activation: microRNAs can up-regulate translation. Science. 2007; 318(5858):1931-4. DOI: 10.1126/science.1149460. View

14.

Wang W, Wang X, Ward A, Touw I, Friedman A . C/EBPalpha and G-CSF receptor signals cooperate to induce the myeloperoxidase and neutrophil elastase genes. Leukemia. 2001; 15(5):779-86. DOI: 10.1038/sj.leu.2402094. View

15.

Hoover R, GERLACH M, Koh E, Daley G . Cooperative and redundant effects of STAT5 and Ras signaling in BCR/ABL transformed hematopoietic cells. Oncogene. 2001; 20(41):5826-35. DOI: 10.1038/sj.onc.1204549. View

16.

Brown V, Jin P, Ceman S, Darnell J, ODonnell W, Tenenbaum S . Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell. 2001; 107(4):477-87. DOI: 10.1016/s0092-8674(01)00568-2. View

17.

Darnell J, Jensen K, Jin P, Brown V, Warren S, Darnell R . Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell. 2001; 107(4):489-99. DOI: 10.1016/s0092-8674(01)00566-9. View

18.

Perrotti D, Cesi V, Trotta R, Guerzoni C, Santilli G, Campbell K . BCR-ABL suppresses C/EBPalpha expression through inhibitory action of hnRNP E2. Nat Genet. 2001; 30(1):48-58. DOI: 10.1038/ng791. View

19.

Makeyev A, Liebhaber S . The poly(C)-binding proteins: a multiplicity of functions and a search for mechanisms. RNA. 2002; 8(3):265-78. PMC: 1370249. DOI: 10.1017/s1355838202024627. View

20.

Nieborowska-Skorska M, Hoser G, Kossev P, Wasik M, Skorski T . Complementary functions of the antiapoptotic protein A1 and serine/threonine kinase pim-1 in the BCR/ABL-mediated leukemogenesis. Blood. 2002; 99(12):4531-9. DOI: 10.1182/blood.v99.12.4531. View