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PMID: 20805360 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Polyamines regulate the stability of JunD mRNA by modulating the competitive binding of its 3' untranslated region to HuR and AUF1.

Molecular and cellular biology ·Vol. 30 ·No. 21 ·2010-11-00 ·Pages 5021-32

Zou T, Rao JN, Liu L, Xiao L, Yu TX, Jiang P, Gorospe M, Wang JY

Abstract

Polyamines critically regulate all mammalian cell growth and proliferation by mechanisms such as the repression of growth-inhibitory proteins, including JunD. Decreasing the levels of cellular polyamines stabilizes JunD mRNA without affecting its transcription, but the exact mechanism whereby polyamines regulate JunD mRNA degradation has not been elucidated. RNA-binding proteins HuR and AUF1 associate with labile mRNAs bearing AU-rich elements located in the 3' untranslated regions (3'-UTRs) and modulate their stability. Here, we show that JunD mRNA is a target of HuR and AUF1 and that polyamines modulate JunD mRNA degradation by altering the competitive binding of HuR and AUF1 to the JunD 3'-UTR. The depletion of cellular polyamines enhanced HuR binding to JunD mRNA and decreased the levels of JunD transcript associated with AUF1, thus stabilizing JunD mRNA. The silencing of HuR increased AUF1 binding to the JunD mRNA, decreased the abundance of HuR-JunD mRNA complexes, rendered the JunD mRNA unstable, and prevented increases in JunD mRNA and protein in polyamine-deficient cells. Conversely, increasing the cellular polyamines repressed JunD mRNA interaction with HuR and enhanced its association with AUF1, resulting in an inhibition of JunD expression. These results indicate that polyamines modulate the stability of JunD mRNA in intestinal epithelial cells through HuR and AUF1 and provide new insight into the molecular functions of cellular polyamines.

MeSH Terms
3' Untranslated Regions Animals Antigens, Surface/genetics,metabolism Base Sequence Binding Sites/genetics Binding, Competitive Caco-2 Cells Cell Line DNA Primers/genetics ELAV Proteins ELAV-Like Protein 1 Genes, jun Heterogeneous Nuclear Ribonucleoprotein D0 Heterogeneous-Nuclear Ribonucleoprotein D/antagonists & inhibitors,genetics,metabolism Humans Molecular Sequence Data Polyamines/metabolism RNA Interference RNA Stability RNA, Messenger/genetics,metabolism RNA, Small Interfering/genetics RNA-Binding Proteins/antagonists & inhibitors,genetics,metabolism Rats Sequence Deletion
Chemicals
3' Untranslated Regions Antigens, Surface DNA Primers ELAV Proteins ELAV-Like Protein 1 ELAVL1 protein, human HNRNPD protein, human Heterogeneous Nuclear Ribonucleoprotein D0 Heterogeneous-Nuclear Ribonucleoprotein D Hnrnpd protein, rat Polyamines RNA, Messenger RNA, Small Interfering RNA-Binding Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Zou Tongtong
Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Rao Jaladanki N
Liu Lan
Xiao Lan
Yu Ting-Xi
Jiang Ping
Gorospe Myriam
Wang Jian-Ying
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.00807-10
Published
2010-11-00
Epub
2010-00-30
Pages
5021-32
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2953062
Subset
IM
Grants
NIDDK NIH HHS · DK-57819 · United States
NIDDK NIH HHS · DK-61972 · United States
NIDDK NIH HHS · R01 DK057819 · United States
NIDDK NIH HHS · DK-68491 · United States
NIDDK NIH HHS · R01 DK068491 · United States
NIDDK NIH HHS · R01 DK061972 · United States
External Links
PubMed source DOI: 10.1128/MCB.00807-10 PMC Full Text View journal details
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