AUF1 p42 isoform selectively controls both steady-state and PGE2-induced FGF9 mRNA decay

Tsung Ming Chen, Chien Hui Hsu, Shaw-Jenq Tsai, Hsiao-Fang Sun

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Fibroblast growth factor 9 (FGF9) is an autocrine/paracrine growth factor that plays vital roles in many physiologic processes including embryonic development. Aberrant expression of FGF9 causes human diseases and thus it highlights the importance of controlling FGF9 expression; however, the mechanism responsible for regulation of FGF9 expression is largely unknown. Here, we show the crucial role of an AU-rich element (ARE) in FGF9 3′-untranslated region (UTR) on controlling FGF9 expression. Our data demonstrated that AUF1 binds to this ARE to regulate FGF9 mRNA stability. Overexpression of each isoform of AUF1 (p37, p40, p42 and p45) showed that only the p42 isoform reduced the steady-state FGF9 mRNA. Also, knockdown of p42AUF1 prolonged the half-life of FGF9 mRNA. The induction of FGF9 mRNA in prostaglandin (PG) E2-treated human endometrial stromal cells was accompanied with declined cytoplasmic AUF1. Nevertheless, ablation of AUF1 led to sustained elevation of FGF9 expression in these cells. Our study demonstrated that p42AUF1 regulates both steady-state and PGE2-induced FGF9 mRNA stability through ARE-mediated mRNA degradation. Since almost half of the FGF family members are ARE-containing genes, our findings also suggest that ARE-mediated mRNA decay is a common pathway to control FGFs expression, and it represents a novel RNA regulon to coordinate FGFs homeostasis in various physiological conditions.

Original languageEnglish
Pages (from-to)8061-8071
Number of pages11
JournalNucleic acids research
Volume38
Issue number22
DOIs
Publication statusPublished - 2010 Dec 1

Fingerprint

Fibroblast Growth Factor 9
RNA Stability
Dinoprostone
Protein Isoforms
AU Rich Elements
Messenger RNA
Fibroblast Growth Factor 3
Regulon
3' Untranslated Regions
Stromal Cells

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

@article{699c6ada56fd4baa9f7262f48f1408bb,
title = "AUF1 p42 isoform selectively controls both steady-state and PGE2-induced FGF9 mRNA decay",
abstract = "Fibroblast growth factor 9 (FGF9) is an autocrine/paracrine growth factor that plays vital roles in many physiologic processes including embryonic development. Aberrant expression of FGF9 causes human diseases and thus it highlights the importance of controlling FGF9 expression; however, the mechanism responsible for regulation of FGF9 expression is largely unknown. Here, we show the crucial role of an AU-rich element (ARE) in FGF9 3′-untranslated region (UTR) on controlling FGF9 expression. Our data demonstrated that AUF1 binds to this ARE to regulate FGF9 mRNA stability. Overexpression of each isoform of AUF1 (p37, p40, p42 and p45) showed that only the p42 isoform reduced the steady-state FGF9 mRNA. Also, knockdown of p42AUF1 prolonged the half-life of FGF9 mRNA. The induction of FGF9 mRNA in prostaglandin (PG) E2-treated human endometrial stromal cells was accompanied with declined cytoplasmic AUF1. Nevertheless, ablation of AUF1 led to sustained elevation of FGF9 expression in these cells. Our study demonstrated that p42AUF1 regulates both steady-state and PGE2-induced FGF9 mRNA stability through ARE-mediated mRNA degradation. Since almost half of the FGF family members are ARE-containing genes, our findings also suggest that ARE-mediated mRNA decay is a common pathway to control FGFs expression, and it represents a novel RNA regulon to coordinate FGFs homeostasis in various physiological conditions.",
author = "Chen, {Tsung Ming} and Hsu, {Chien Hui} and Shaw-Jenq Tsai and Hsiao-Fang Sun",
year = "2010",
month = "12",
day = "1",
doi = "10.1093/nar/gkq717",
language = "English",
volume = "38",
pages = "8061--8071",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "22",

}

AUF1 p42 isoform selectively controls both steady-state and PGE2-induced FGF9 mRNA decay. / Chen, Tsung Ming; Hsu, Chien Hui; Tsai, Shaw-Jenq; Sun, Hsiao-Fang.

In: Nucleic acids research, Vol. 38, No. 22, 01.12.2010, p. 8061-8071.

Research output: Contribution to journalArticle

TY - JOUR

T1 - AUF1 p42 isoform selectively controls both steady-state and PGE2-induced FGF9 mRNA decay

AU - Chen, Tsung Ming

AU - Hsu, Chien Hui

AU - Tsai, Shaw-Jenq

AU - Sun, Hsiao-Fang

PY - 2010/12/1

Y1 - 2010/12/1

N2 - Fibroblast growth factor 9 (FGF9) is an autocrine/paracrine growth factor that plays vital roles in many physiologic processes including embryonic development. Aberrant expression of FGF9 causes human diseases and thus it highlights the importance of controlling FGF9 expression; however, the mechanism responsible for regulation of FGF9 expression is largely unknown. Here, we show the crucial role of an AU-rich element (ARE) in FGF9 3′-untranslated region (UTR) on controlling FGF9 expression. Our data demonstrated that AUF1 binds to this ARE to regulate FGF9 mRNA stability. Overexpression of each isoform of AUF1 (p37, p40, p42 and p45) showed that only the p42 isoform reduced the steady-state FGF9 mRNA. Also, knockdown of p42AUF1 prolonged the half-life of FGF9 mRNA. The induction of FGF9 mRNA in prostaglandin (PG) E2-treated human endometrial stromal cells was accompanied with declined cytoplasmic AUF1. Nevertheless, ablation of AUF1 led to sustained elevation of FGF9 expression in these cells. Our study demonstrated that p42AUF1 regulates both steady-state and PGE2-induced FGF9 mRNA stability through ARE-mediated mRNA degradation. Since almost half of the FGF family members are ARE-containing genes, our findings also suggest that ARE-mediated mRNA decay is a common pathway to control FGFs expression, and it represents a novel RNA regulon to coordinate FGFs homeostasis in various physiological conditions.

AB - Fibroblast growth factor 9 (FGF9) is an autocrine/paracrine growth factor that plays vital roles in many physiologic processes including embryonic development. Aberrant expression of FGF9 causes human diseases and thus it highlights the importance of controlling FGF9 expression; however, the mechanism responsible for regulation of FGF9 expression is largely unknown. Here, we show the crucial role of an AU-rich element (ARE) in FGF9 3′-untranslated region (UTR) on controlling FGF9 expression. Our data demonstrated that AUF1 binds to this ARE to regulate FGF9 mRNA stability. Overexpression of each isoform of AUF1 (p37, p40, p42 and p45) showed that only the p42 isoform reduced the steady-state FGF9 mRNA. Also, knockdown of p42AUF1 prolonged the half-life of FGF9 mRNA. The induction of FGF9 mRNA in prostaglandin (PG) E2-treated human endometrial stromal cells was accompanied with declined cytoplasmic AUF1. Nevertheless, ablation of AUF1 led to sustained elevation of FGF9 expression in these cells. Our study demonstrated that p42AUF1 regulates both steady-state and PGE2-induced FGF9 mRNA stability through ARE-mediated mRNA degradation. Since almost half of the FGF family members are ARE-containing genes, our findings also suggest that ARE-mediated mRNA decay is a common pathway to control FGFs expression, and it represents a novel RNA regulon to coordinate FGFs homeostasis in various physiological conditions.

UR - http://www.scopus.com/inward/record.url?scp=78650451949&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650451949&partnerID=8YFLogxK

U2 - 10.1093/nar/gkq717

DO - 10.1093/nar/gkq717

M3 - Article

VL - 38

SP - 8061

EP - 8071

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 22

ER -