miR-328 Functions as an RNA Decoy to Modulate hnRNP E2 Regulation of mRNA Translation in Leukemic Blasts | Zendy

Anna M. Eiring | Zendy; Jason G. Harb | Zendy; Paolo Neviani | Zendy; Christopher Garton | Zendy; Joshua J. Oaks | Zendy; Riccardo Spizzo | Zendy; Shujun Liu | Zendy; Sebastian Schwind | Zendy; Ramasamy Santhanam | Zendy; Christopher Hickey | Zendy; Heiko Becker | Zendy; Jason C. Chandler | Zendy; Raul Andino | Zendy; Jorge E. Cortés | Zendy; Peter Hokland | Zendy; Claudia S. Huettner | Zendy; Ravi Bhatia | Zendy; Denis Roy | Zendy; Stephen A. Liebhaber | Zendy; Michael A. Caligiuri | Zendy; Guido Marcucci | Zendy; Ramiro Garzon | Zendy; Carlo M. Croce | Zendy; George A. Calin | Zendy; Danilo Perrotti | Zendy

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miR-328 Functions as an RNA Decoy to Modulate hnRNP E2 Regulation of mRNA Translation in Leukemic Blasts

Author(s) -

Anna M. Eiring,

Jason G. Harb,

Paolo Neviani,

Christopher Garton,

Joshua J. Oaks,

Riccardo Spizzo,

Shujun Liu,

Sebastian Schwind,

Ramasamy Santhanam,

Christopher Hickey,

Heiko Becker,

Jason C. Chandler,

Raul Andino,

Jorge E. Cortés,

Peter Hokland,

Claudia S. Huettner,

Ravi Bhatia,

Denis Roy,

Stephen A. Liebhaber,

Michael A. Caligiuri,

Guido Marcucci,

Ramiro Garzon,

Carlo M. Croce,

George A. Calin,

Danilo Perrotti

Publication year - 2010

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2010.01.007

Subject(s) - biology , translation (biology) , rna binding protein , messenger rna , heterogeneous nuclear ribonucleoprotein , heterogeneous ribonucleoprotein particle , microbiology and biotechnology , three prime untranslated region , microrna , rna , ribonucleoprotein , untranslated region , genetics , gene

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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