Polypyrimidine tract-binding protein interacts with coxsackievirus B3 RNA and influences its translation

被引:32
作者
Verma, Bhupendra [1 ]
Bhattacharyya, Sankar [1 ]
Das, Saumitra [1 ]
机构
[1] Indian Inst Sci, Dept Microbiol & Cell Biol, Bangalore 560012, Karnataka, India
关键词
RIBOSOME ENTRY SITE; MOUTH-DISEASE VIRUS; 5 NONTRANSLATED REGION; HEPATITIS-A VIRUS; ENCEPHALOMYOCARDITIS VIRUS; 5'-UNTRANSLATED REGION; MEDIATED TRANSLATION; INTERNAL INITIATION; MULTIPLE SITES; IRES;
D O I
10.1099/vir.0.018507-0
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
We have investigated the possible role of trans-acting factors interacting with the untranslated regions (UTRs) of coxsackievirus B3 (CVB3) RNA. We show here that polypyrimidine tract-binding protein (PTB) binds specifically to both 5' and 3' UTRs, but with different affinity. We have demonstrated that PTB is a bona fide internal ribosome entry site (IRES) trans-acting factor (ITAF) for CVB3 RNA by characterizing the effect of partial silencing of FIB ex vivo in He La cells. Furthermore, IRES activity in BSC-1 cells, which are reported to have a very low level of endogenous FIB, was found to be significantly lower than that in He La cells. Additionally, we have mapped the putative contact points of PTB on the 5' and 3' UTRs by an RNA toe-printing assay. We have shown that the 3' UTR is able to stimulate CVB3 IRES-mediated translation. Interestingly, a deletion of 15 nt at the 5' end or 14 rut at the 3' end of the CVB3 3' UTR reduced the 3' UTR-mediated enhancement of IRES activity ex vivo significantly, and a reduced interaction was shown with PTB. It appears that the FIB protein might help in circularization of the CVB3 RNA by bridging the ends necessary for efficient translation of the viral RNA.
引用
收藏
页码:1245 / 1255
页数:11
相关论文
共 30 条
[1]  
Baboonian C, 1997, CURR TOP MICROBIOL, V223, P31
[2]   The substitution U475→C with Sabin3-like mutation within the IRES attenuate Coxsackievirus B3 cardiovirulence [J].
Ben M'hadheb-Gharbi, Manel ;
Paulous, Sylvie ;
Aouni, Mahjoub ;
Kean, Katherine M. ;
Gharbi, Jawhar .
MOLECULAR BIOTECHNOLOGY, 2007, 36 (01) :52-60
[3]   Mapping of secondary structure of the spacer region within the 5′-untranslated region of the coxsackievirus B3 RNA:: possible role of an apical GAGA loop in binding La protein and influencing internal initiation of translation [J].
Bhattacharyya, S ;
Das, S .
VIRUS RESEARCH, 2005, 108 (1-2) :89-100
[4]  
Bhattacharyya Sankar, 2006, RNA Biol, V3, P60
[5]   The structure and function of a cis-acting element located upstream of the IRES that influences Coxsackievirus B3 RNA translation [J].
Bhattacharyya, Sankar ;
Verma, Bhupendra ;
Pandey, Gaurav ;
Das, Saumitra .
VIROLOGY, 2008, 377 (02) :343-352
[6]   Development of antiviral agents for enteroviruses [J].
Chen, Tzu-Chun ;
Weng, Kuo-Feng ;
Chang, Shih-Cheng ;
Lin, Jing-Yi ;
Huang, Peng-Nien ;
Shih, Shin-Ru .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2008, 62 (06) :1169-1173
[7]   Translational control of the interferon regulatory factor 2 mRNA by IRES element [J].
Dhar, Debojyoti ;
Roy, Swagata ;
Das, Saumitra .
NUCLEIC ACIDS RESEARCH, 2007, 35 (16) :5409-5421
[8]   Competitive translation efficiency at the picornavirus type 1 internal ribosome entry site facilitated by viral cis and trans factors [J].
Dobrikova, EY ;
Grisham, RN ;
Kaiser, C ;
Lin, J ;
Gromeier, M .
JOURNAL OF VIROLOGY, 2006, 80 (07) :3310-3321
[9]   Bridging IRES elements in mRNAs to the eukaryotic translation apparatus [J].
Fitzgerald, Kerry D. ;
Semler, Bert L. .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2009, 1789 (9-10) :518-528
[10]   Transient expression of cellular polypyrimidine-tract binding protein stimulates cap-independent translation directed by both picornaviral and flaviviral internal ribosome entry sites in vivo [J].
Gosert, R ;
Chang, KH ;
Rijnbrand, R ;
Yi, MY ;
Sangar, DV ;
Lemon, SM .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (05) :1583-1595