c-Myc-regulated microRNAs modulate E2F1 expression

Kathryn A O'Donnell-Mendell, Erik A. Wentzel, Karen I. Zeller, Chi V. Dang, Joshua T Mendell

Research output: Contribution to journalArticle

2235 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) are 21-23 nucleotide RNA molecules that regulate the stability or translational efficiency of target messenger RNAs. miRNAs have diverse functions, including the regulation of cellular differentiation, proliferafion and apoptosis. Although strict tissue- and developmental-stage- specific expression is critical for appropriate miRNA function, mammalian transcription factors that regulate miRNAs have not yet been identified. The proto-oncogene c-MYC encodes a transcription factor that regulates cell proliferation, growth and apoptosis. Dysregulated expression or function of c-Myc is one of the most common abnormalities in human malignancy. Here we show that c-Myc activates expression of a cluster of six miRNAs on human chromosome 13. Chromatin immunoprecipation experiments show that c-Myc binds directly to this locus. The transcription factor E2F1 is an additional target of c-Myc that promotes cell cycle progression. We find that expression of E2F1 is negatively regulated by two miRNAs in this cluster, miR-17-5p and miR-20a. These findings expand the known classes of transcripts within the c-Myc target gene network, and reveal a mechanism through which c-Myc simultaneously activates E2F1 transcription and limits its translation, allowing a tightly controlled proliferative signal.

Original languageEnglish (US)
Pages (from-to)839-843
Number of pages5
JournalNature
Volume435
Issue number7043
DOIs
StatePublished - Jun 9 2005

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MicroRNAs
Transcription Factors
E2F1 Transcription Factor
Apoptosis
Chromosomes, Human, Pair 13
myc Genes
Proto-Oncogenes
Gene Regulatory Networks
Human Chromosomes
Chromatin
Cell Cycle
Nucleotides
Cell Proliferation
RNA
Messenger RNA
Growth
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

c-Myc-regulated microRNAs modulate E2F1 expression. / O'Donnell-Mendell, Kathryn A; Wentzel, Erik A.; Zeller, Karen I.; Dang, Chi V.; Mendell, Joshua T.

In: Nature, Vol. 435, No. 7043, 09.06.2005, p. 839-843.

Research output: Contribution to journalArticle

O'Donnell-Mendell, Kathryn A ; Wentzel, Erik A. ; Zeller, Karen I. ; Dang, Chi V. ; Mendell, Joshua T. / c-Myc-regulated microRNAs modulate E2F1 expression. In: Nature. 2005 ; Vol. 435, No. 7043. pp. 839-843.
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