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Molecular and Cellular Biology, May 2009, p. 2841-2851, Vol. 29, No. 10
0270-7306/09/$08.00+0     doi:10.1128/MCB.01971-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

miR-181a Regulates Cap-Dependent Translation of p27kip1 mRNA in Myeloid Cells{triangledown}

Rafael Cuesta,*§ Aida Martínez-Sánchez,§ and Fátima Gebauer*

Centre de Regulació Genòmica (CRG-UPF), Gene Regulation Programme, Dr. Aiguader 88, 08003 Barcelona, Spain

Received 31 December 2008/ Returned for modification 3 February 2009/ Accepted 23 February 2009

p27kip1 (p27) is a cell cycle inhibitor and tumor suppressor whose expression is tightly regulated in the cell. Translational control of p27 mRNA has emerged as a prominent mechanism to regulate p27 expression during differentiation, quiescence, and cancer progression. The microRNAs miR-221 and miR-222 repress p27 expression in various cancer cells, and this repression promotes tumor cell proliferation. In addition, the presence of an internal ribosome entry site in the 5' untranslated region (UTR) of p27 mRNA has been reported. Here, we show that p27 mRNA is translated via a cap-dependent mechanism in HeLa and HL60 cells and that the previously reported IRES activity can be attributed to cryptic promoters in the sequence corresponding to the p27 5' UTR. Furthermore, cap-dependent translation of p27 mRNA is repressed by miR-181a in undifferentiated HL60 cells. Repression by miR-181a is relieved during differentiation of HL60 into monocyte-like cells, allowing the accumulation of p27, which is necessary to fully block cell cycle progression and reach terminal differentiation. These results identify miR-181a as a regulator of p27 mRNA translation during myeloid cell differentiation.

* Corresponding author. Mailing address for Fátima Geloaver: Centre de Regulació Genòmica (CRG-UPF), Gene Regulation Programme, Dr. Aiguader 88, 08003 Barcelona, Spain. Phone: 34-93 3160120. Fax: 34-93 3969983. E-mail: fatima.gebauer{at}crg.es. Present address for Rafael Cuesta: Department of Microbiology, NYU School of Medicine, 550 First Avenue, New York NY 10016. Phone: (212) 263-6007. Fax: (212) 263-8276. E-mail: cuestr01{at}nyumc.org

{triangledown} Published ahead of print on 9 March 2009.

§ R.C. and A.M.-S. contributed equally to this study.

Molecular and Cellular Biology, May 2009, p. 2841-2851, Vol. 29, No. 10
0270-7306/09/$08.00+0     doi:10.1128/MCB.01971-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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