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：13

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

来源：

FEBS JOURNAL | 2016年 / 283卷 / 10期

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.

引用

页码：1880 / 1901

页数：22

共 92 条

[1] Structural basis of genomic RNA (gRNA) dimerization and packaging determinants of mouse mammary tumor virus (MMTV) [J].