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Phosphorylation of the human microRNA-generating complex mediates MAPK/Erk signaling
- Source :
- Cell. 139(1)
- Publication Year :
- 2009
-
Abstract
- SummaryMicroRNAs (miRNAs) govern an expanding number of biological and disease processes. Understanding the mechanisms by which the miRNA pathway is regulated, therefore, represents an important area of investigation. We determined that the human miRNA-generating complex is comprised of Dicer and phospho-TRBP isoforms. Phosphorylation of TRBP is mediated by the mitogen-activated protein kinase (MAPK) Erk. Expression of phospho-mimic TRBP and TRBP phosphorylation enhanced miRNA production by increasing stability of the miRNA-generating complex. Mitogenic signaling in response to serum and the tumor promoter PMA was dependent on TRBP phosphorylation. These effects were accompanied by a coordinated increase in levels of growth-promoting miRNA and reduced expression of let-7 tumor suppressor miRNA. Conversely, pharmacological inhibition of MAPK/Erk resulted in an anti-growth miRNA profile. Taken together, these studies indicate that the MAPK/Erk pathway regulates the miRNA machinery and suggest a general principle, wherein signaling systems target the miRNA pathway to achieve biological responses.
- Subjects :
- MAPK/ERK pathway
Gene isoform
Ribonuclease III
MAP Kinase Signaling System
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
microRNA
Humans
Protein Isoforms
Phosphorylation
Protein kinase A
030304 developmental biology
Regulation of gene expression
0303 health sciences
biology
Biochemistry, Genetics and Molecular Biology(all)
RNA-Binding Proteins
Cell biology
MicroRNAs
Gene Expression Regulation
SIGNALING
030220 oncology & carcinogenesis
biology.protein
Cancer research
RNA
CELLBIO
Dicer
HeLa Cells
Subjects
Details
- ISSN :
- 10974172
- Volume :
- 139
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....3980687fb90e5bafa9219afb55f8a99f