title: Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression.
abstract: microRNAs (miRNAs) are abundant, approximately 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 G(0)/G(1). 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.
authors.affiliation: Rosetta Inpharmatics, LLC, 401 Terry Ave. N, Seattle, WA 98109, USA. peter_linsley@merck.com
authors.forename: Peter S
authors.initials: PS
authors.lastname: Linsley
authors.forename: Janell
authors.initials: J
authors.lastname: Schelter
authors.forename: Julja
authors.initials: J
authors.lastname: Burchard
authors.forename: Miho
authors.initials: M
authors.lastname: Kibukawa
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Martin
authors.forename: Steven R
authors.initials: SR
authors.lastname: Bartz
authors.forename: Jason M
authors.initials: JM
authors.lastname: Johnson
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Cummins
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Raymond
authors.forename: Hongyue
authors.initials: H
authors.lastname: Dai
authors.forename: Nelson
authors.initials: N
authors.lastname: Chau
authors.forename: Michele
authors.initials: M
authors.lastname: Cleary
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Jackson
authors.forename: Michael
authors.initials: M
authors.lastname: Carleton
authors.forename: Lee
authors.initials: L
authors.lastname: Lim
mesh_terms: D002453:Cell Cycle / Q000235:genetics* / Q000502:physiology*; D002460:Cell Line; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000145:classification* / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D014158:Transcription, Genetic
chemical_list: D035683:MicroRNAs