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PMID: 19804757 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Phosphorylation of the human microRNA-generating complex mediates MAPK/Erk signaling.

Cell ·Vol. 139 ·No. 1 ·2009-10-02 ·Pages 112-22

Paroo Z, Ye X, Chen S, Liu Q

Abstract

MicroRNAs (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.

MeSH Terms
Gene Expression Regulation HeLa Cells Humans MAP Kinase Signaling System MicroRNAs/metabolism Phosphorylation Protein Isoforms/metabolism RNA-Binding Proteins/metabolism Ribonuclease III/metabolism
Chemicals
MicroRNAs Protein Isoforms RNA-Binding Proteins trans-activation responsive RNA-binding protein Ribonuclease III
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Paroo Zain
Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Ye Xuecheng
Chen She
Liu Qinghua
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2009.06.044
Published
2009-10-02
Pages
112-22
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2760040
Subset
IM
Grants
NCRR NIH HHS · C06 RR015437 · United States
NIGMS NIH HHS · GM 084010 · United States
NIGMS NIH HHS · R01 GM078163-03 · United States
NIGMS NIH HHS · R01 GM084010-01 · United States
NCRR NIH HHS · C06-RR15437-01 · United States
NIGMS NIH HHS · R01 GM078163-02 · United States
NIGMS NIH HHS · GM 078163 · United States
NIGMS NIH HHS · R01 GM078163 · United States
NIGMS NIH HHS · R01 GM084010 · United States
NIGMS NIH HHS · R01 GM084010-01S1 · United States
NIGMS NIH HHS · R01 GM078163-01 · United States
Databases
GEO
GSE16442
Corrections
CommentIn
PMID: 19804751
External Links
PubMed source DOI: 10.1016/j.cell.2009.06.044 PMC Full Text View journal details
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