共 34 条
Polypyrimidine tract-binding protein binds to the 5 untranslated region of the mouse mammary tumor virus mRNA and stimulates cap-independent translation initiation
被引:14
|作者:
Caceres, Carlos J.
[1
]
Contreras, Nataly
[1
]
Angulo, Jenniffer
[1
]
Vera-Otarola, Jorge
[1
]
Pino-Ajenjo, Constanza
[1
]
Llorian, Miriam
[2
]
Ameur, Melissa
[3
]
Lisboa, Francisco
[1
]
Pino, Karla
[1
]
Lowy, Fernando
[1
]
Sargueil, Bruno
[3
]
Lopez-Lastra, Marcelo
[1
]
机构:
[1] Pontificia Univ Catolica Chile, Inst Milenio Inmunol & Inmunoterapia, Dept Enfermedades Infecciosas & Inmunol Pediat, Lab Virol Mol,Ctr Invest Med,Escuela Med, Alameda 340, Santiago, Chile
[2] Univ Cambridge, Dept Biochem, Cambridge CB2 1TN, England
[3] Univ Paris 05, CNRS, Lab Cristallog & RMN Biol, Unite Mixte Rech 8015, Paris, France
基金:
英国惠康基金;
关键词:
internal ribosomal entry site;
IRES trans-acting factor;
mouse mammary tumor virus;
polypyrimidine tract-binding protein;
RIBOSOME ENTRY SITE;
TRANS-ACTING FACTORS;
INTERNAL INITIATION;
BREAST-CANCER;
FUNCTIONAL REQUIREMENT;
MEDIATED TRANSLATION;
GENE-EXPRESSION;
CELL-GROWTH;
PTB;
IRES;
D O I:
10.1111/febs.13708
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
The 5 untranslated region (UTR) of the full-length mRNA of the mouse mammary tumor virus (MMTV) harbors an internal ribosomal entry site (IRES). In this study, we show that the polypyrimidine tract-binding protein (PTB), an RNA-binding protein with four RNA recognition motifs (RRMs), binds to the MMTV 5 UTR stimulating its IRES activity. There are three isoforms of PTB: PTB1, PTB2, and PTB4. Results show that PTB1 and PTB4, but not PTB2, stimulate MMTV-IRES activity. PTB1 promotes MMTV-IRES-mediated initiation more strongly than PTB4. When expressed in combination, PTB1 further enhanced PTB4 stimulation of the MMTV-IRES, while PTB2 fully abrogates PTB4-induced stimulation. PTB1-induced stimulation of MMTV-IRES was not altered in the presence of PTB4 or PTB2. Mutational analysis reveals that stimulation of MMTV-IRES activity is abrogated when PTB1 is mutated either in RRM1/RRM2 or RRM3/RRM4. In contrast, a PTB4 RRM1/RRM2 mutant has reduced effect over MMTV-IRES activity, while stimulation of the MMTV-IRES activity is still observed when the PTB4 RRM3/RMM4 mutant is used. Therefore, PTB1 and PTB4 differentially stimulate the IRES activity. In contrast, PTB2 acts as a negative modulator of PTB4-induced stimulation of MMTV-IRES. We conclude that PTB1 and PTB4 act as IRES trans-acting factors of the MMTV-IRES.
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页码:1880 / 1901
页数:22
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