RNA-binding protein HuR interacts with thrombomodulin 5′untranslated region and represses internal ribosome entry site-mediated translation under IL-1β treatment

Chiu Hung Yeh, Liang Y. Hung, Chin Hsu, Shu Y. Le, Pin T. Lee, Wan L. Liao, Yi Tseng Lin, Wen Chang Chang, Joseph T. Tseng

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Reduction in host-activated protein C levels and resultant microvascular thrombosis highlight the important functional role of protein C anticoagulant system in the pathogenesis of sepsis and septic shock. Thrombomodulin (TM) is a critical factor to activate protein C in mediating the anticoagulation and anti-inflammation effects. However, TM protein content is decreased in inflammation and sepsis, and the mechanism is still not well defined. In this report, we identified that the TM 5′ untranslated region (UTR) bearing the internal ribosome entry site (IRES) element controls TM protein expression. Using RNA probe pulldown assay, HuR was demonstrated to interact with the TM 5′UTR. Overexpression of HuR protein inhibited the activity of TM IRES, whereas on the other hand, reducing the HuR protein level reversed this effect. When cells were treated with IL-1β, the IRES activity was suppressed and accompanied by an increased interaction between HuR and TM 5′UTR. In the animal model of sepsis, we found the TM protein expression level to be decreased while concurrently observing the increased interaction between HuR and TM mRNA in liver tissue. In summary, HuR plays an important role in suppression of TM protein synthesis in IL-1β treatment and sepsis.

Original languageEnglish
Pages (from-to)3812-3822
Number of pages11
JournalMolecular Biology of the Cell
Volume19
Issue number9
DOIs
Publication statusPublished - Sep 2008
Externally publishedYes

Fingerprint

Thrombomodulin
RNA-Binding Proteins
Interleukin-1
Sepsis
Protein C
Proteins
Internal Ribosome Entry Sites
Inflammation
RNA Probes
5' Untranslated Regions
Septic Shock
Anticoagulants
Thrombosis
Animal Models

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

RNA-binding protein HuR interacts with thrombomodulin 5′untranslated region and represses internal ribosome entry site-mediated translation under IL-1β treatment. / Yeh, Chiu Hung; Hung, Liang Y.; Hsu, Chin; Le, Shu Y.; Lee, Pin T.; Liao, Wan L.; Lin, Yi Tseng; Chang, Wen Chang; Tseng, Joseph T.

In: Molecular Biology of the Cell, Vol. 19, No. 9, 09.2008, p. 3812-3822.

Research output: Contribution to journalArticle

Yeh, Chiu Hung ; Hung, Liang Y. ; Hsu, Chin ; Le, Shu Y. ; Lee, Pin T. ; Liao, Wan L. ; Lin, Yi Tseng ; Chang, Wen Chang ; Tseng, Joseph T. / RNA-binding protein HuR interacts with thrombomodulin 5′untranslated region and represses internal ribosome entry site-mediated translation under IL-1β treatment. In: Molecular Biology of the Cell. 2008 ; Vol. 19, No. 9. pp. 3812-3822.
@article{b909f016a2ea4a1aa7ff766512a45b82,
title = "RNA-binding protein HuR interacts with thrombomodulin 5′untranslated region and represses internal ribosome entry site-mediated translation under IL-1β treatment",
abstract = "Reduction in host-activated protein C levels and resultant microvascular thrombosis highlight the important functional role of protein C anticoagulant system in the pathogenesis of sepsis and septic shock. Thrombomodulin (TM) is a critical factor to activate protein C in mediating the anticoagulation and anti-inflammation effects. However, TM protein content is decreased in inflammation and sepsis, and the mechanism is still not well defined. In this report, we identified that the TM 5′ untranslated region (UTR) bearing the internal ribosome entry site (IRES) element controls TM protein expression. Using RNA probe pulldown assay, HuR was demonstrated to interact with the TM 5′UTR. Overexpression of HuR protein inhibited the activity of TM IRES, whereas on the other hand, reducing the HuR protein level reversed this effect. When cells were treated with IL-1β, the IRES activity was suppressed and accompanied by an increased interaction between HuR and TM 5′UTR. In the animal model of sepsis, we found the TM protein expression level to be decreased while concurrently observing the increased interaction between HuR and TM mRNA in liver tissue. In summary, HuR plays an important role in suppression of TM protein synthesis in IL-1β treatment and sepsis.",
author = "Yeh, {Chiu Hung} and Hung, {Liang Y.} and Chin Hsu and Le, {Shu Y.} and Lee, {Pin T.} and Liao, {Wan L.} and Lin, {Yi Tseng} and Chang, {Wen Chang} and Tseng, {Joseph T.}",
year = "2008",
month = "9",
doi = "10.1091/mbc.E07-09-0962",
language = "English",
volume = "19",
pages = "3812--3822",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "9",

}

TY - JOUR

T1 - RNA-binding protein HuR interacts with thrombomodulin 5′untranslated region and represses internal ribosome entry site-mediated translation under IL-1β treatment

AU - Yeh, Chiu Hung

AU - Hung, Liang Y.

AU - Hsu, Chin

AU - Le, Shu Y.

AU - Lee, Pin T.

AU - Liao, Wan L.

AU - Lin, Yi Tseng

AU - Chang, Wen Chang

AU - Tseng, Joseph T.

PY - 2008/9

Y1 - 2008/9

N2 - Reduction in host-activated protein C levels and resultant microvascular thrombosis highlight the important functional role of protein C anticoagulant system in the pathogenesis of sepsis and septic shock. Thrombomodulin (TM) is a critical factor to activate protein C in mediating the anticoagulation and anti-inflammation effects. However, TM protein content is decreased in inflammation and sepsis, and the mechanism is still not well defined. In this report, we identified that the TM 5′ untranslated region (UTR) bearing the internal ribosome entry site (IRES) element controls TM protein expression. Using RNA probe pulldown assay, HuR was demonstrated to interact with the TM 5′UTR. Overexpression of HuR protein inhibited the activity of TM IRES, whereas on the other hand, reducing the HuR protein level reversed this effect. When cells were treated with IL-1β, the IRES activity was suppressed and accompanied by an increased interaction between HuR and TM 5′UTR. In the animal model of sepsis, we found the TM protein expression level to be decreased while concurrently observing the increased interaction between HuR and TM mRNA in liver tissue. In summary, HuR plays an important role in suppression of TM protein synthesis in IL-1β treatment and sepsis.

AB - Reduction in host-activated protein C levels and resultant microvascular thrombosis highlight the important functional role of protein C anticoagulant system in the pathogenesis of sepsis and septic shock. Thrombomodulin (TM) is a critical factor to activate protein C in mediating the anticoagulation and anti-inflammation effects. However, TM protein content is decreased in inflammation and sepsis, and the mechanism is still not well defined. In this report, we identified that the TM 5′ untranslated region (UTR) bearing the internal ribosome entry site (IRES) element controls TM protein expression. Using RNA probe pulldown assay, HuR was demonstrated to interact with the TM 5′UTR. Overexpression of HuR protein inhibited the activity of TM IRES, whereas on the other hand, reducing the HuR protein level reversed this effect. When cells were treated with IL-1β, the IRES activity was suppressed and accompanied by an increased interaction between HuR and TM 5′UTR. In the animal model of sepsis, we found the TM protein expression level to be decreased while concurrently observing the increased interaction between HuR and TM mRNA in liver tissue. In summary, HuR plays an important role in suppression of TM protein synthesis in IL-1β treatment and sepsis.

UR - http://www.scopus.com/inward/record.url?scp=55549131174&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55549131174&partnerID=8YFLogxK

U2 - 10.1091/mbc.E07-09-0962

DO - 10.1091/mbc.E07-09-0962

M3 - Article

VL - 19

SP - 3812

EP - 3822

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 9

ER -