The RNA stability regulator HuR regulates L1 protein expression in vivo in differentiating cervical epithelial cells

被引：22

作者：

Cumming, S. A. ^{[1
]}

Chuen-Im, T. ^{[1
]}

Zhang, J. ^{[1
]}

Graham, S. V. ^{[1
]}

机构：

[1] Univ Glasgow, Div Infect & Immun, Fac Biomed & Life Sci, Glasgow G12 8TA, Lanark, Scotland

来源：

VIROLOGY | 2009年 / 383卷 / 01期

基金：

英国生物技术与生命科学研究理事会;

关键词：

HPV16; Late gene expression; Late regulatory element; HuR; Epithelial differentiation; HUMAN-PAPILLOMAVIRUS TYPE-16; MESSENGER-RNA; INHIBITORY-ACTIVITY; BINDING PROTEIN; GENE-EXPRESSION; CODING REGION; ELEMENT; IDENTIFICATION; STABILIZATION; TRANSCRIPTION;

D O I：

10.1016/j.virol.2008.10.003

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Human papillomavirus (HPV) L1 and L2 capsid protein expression is restricted to the granular layer of infected, stratified epithelia and is regulated at least partly at post-transcriptional levels. For HPV16, a 79 nt late regulatory element (LRE) is involved in this control. Using W12 cells as a model for HPV16-infected differentiating cervical epithelial cells we show that HuR, a key cellular protein that controls mRNA stability, binds the LRE most efficiently in nuclear and cytoplasmic extracts of differentiated cells. Further, HuR binds the 3' U-rich portion of the LRE directly in vitro. Overexpression of HuR in undifferentiated W12 cells results in an increase in L1 mRNA and protein levels while siRNA knock-clown of HuR in differentiated W12 cells depletes L1 expression. In differentiated cervical epithelial cells HuR may bind and stabilise L1 mRNAs aiding translation of L1 protein. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：142 / 149

页数：8

共 44 条

[1] Posttranscriptional orchestration of an anti-apoptotic program by HuR [J].

Abdelmohsen, Kotb ;

Lal, Ashish ;

Kim, Hyeon Ho ;

Gorospe, Myriam .

CELL CYCLE, 2007, 6 (11) :1288-1292

[2]

[Anonymous], 1989, Molecular Cloning: A Laboratory Manual

[3]

BEYERFINKLER E, 1990, MED MICROBIOL IMMUN, V179, P185

[4] The alternative splicing factor hnRNP A1 is up-regulated during virus-infected epithelial cell differentiation and binds the human papillomavirus type 16 late regulatory element [J].

Cheunim, Thanaporn ;

Zhang, Jingxin ;

Milligan, Steven G. ;

McPhillips, Maria G. ;

Graham, Sheila V. .

VIRUS RESEARCH, 2008, 131 (02) :189-198

[5] Specific inactivation of inhibitory sequences in the 5′ end of the human papillomavirus type 16 L1 open reading frame results in production of high levels of L1 protein in human epithelial cells [J].

Collier, B ;

Öberg, D ;

Zhao, XM ;

Schwartz, S .

JOURNAL OF VIROLOGY, 2002, 76 (06) :2739-2752

[6] Translational inhibition in vitro of human papillomavirus type 16 L2 mRNA mediated through interaction with heterogenous ribonucleoprotein K and Poly(rC)-binding proteins 1 and 2 [J].

Collier, B ;

Goobar-Larsson, L ;

Sokolowski, M ;

Schwartz, S .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (35) :22648-22656

[7] Activity of the human papillomavirus type 16 late negative regulatory element is partly due to four weak consensus 5′ splice sites that bind a U1 snRNP-like complex [J].

Cumming, SA ;

McPhillips, MG ;

Veerapraditsin, T ;

Milligan, SG ;

Graham, SV .

JOURNAL OF VIROLOGY, 2003, 77 (09) :5167-5177

[8]

Cumming SA, 2005, METH MOLEC MED, V119, P291

[9]

DESILANES IL, 2005, RNA BIOL, V2, pE11

[10] A cellular 65-kDa protein recognizes the negative regulatory element of human papillomavirus late mRNA [J].

DietrichGoetz, W ;

Kennedy, IM ;

Levins, B ;

Stanley, MA ;

Clements, JB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (01) :163-168

← 1 2 3 4 5 →