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Molecular and Cellular Biology, March 2007, p. 2240-2252, Vol. 27, No. 6
0270-7306/07/$08.00+0     doi:10.1128/MCB.02005-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Transcripts Targeted by the MicroRNA-16 Family Cooperatively Regulate Cell Cycle Progression{triangledown} ,{dagger}

Peter S. Linsley,1* Janell Schelter,1 Julja Burchard,1 Miho Kibukawa,1 Melissa M. Martin,1 Steven R. Bartz,1 Jason M. Johnson,1 Jordan M. Cummins,2 Christopher K. Raymond,1 Hongyue Dai,1 Nelson Chau,1 Michele Cleary,1 Aimee L. Jackson,1 Michael Carleton,1 and Lee Lim1

Rosetta Inpharmatics, LLC, Seattle, Washington 98109,1 The Sidney Kimmel Comprehensive Cancer Center and Howard Hughes Medical Institute, Johns Hopkins University Medical Institutions, Baltimore, Maryland 212312

Received 25 October 2006/ Returned for modification 5 December 2006/ Accepted 5 January 2007

microRNAs (miRNAs) are abundant, ~21-nucleotide, noncoding regulatory RNAs. Each miRNA may regulate hundreds of mRNA targets, but the identities of these targets and the processes they regulate are poorly understood. Here we have explored the use of microarray profiling and functional screening to identify targets and biological processes triggered by the transfection of human cells with miRNAs. We demonstrate that a family of miRNAs sharing sequence identity with miRNA-16 (miR-16) negatively regulates cellular growth and cell cycle progression. miR-16-down-regulated transcripts were enriched with genes whose silencing by small interfering RNAs causes an accumulation of cells in G0/G1. Simultaneous silencing of these genes was more effective at blocking cell cycle progression than disruption of the individual genes. Thus, miR-16 coordinately regulates targets that may act in concert to control cell cycle progression.

* Corresponding author. Mailing address: Rosetta Inpharmatics, LLC, 401 Terry Ave. N, Seattle, WA 98109. Phone: (206) 802-7359. Fax: (206) 802-6388. E-mail: peter_linsley{at}merck.com.

{triangledown} Published ahead of print on 22 January 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, March 2007, p. 2240-2252, Vol. 27, No. 6
0270-7306/07/$08.00+0     doi:10.1128/MCB.02005-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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