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The polypyrimidine tract-binding protein stimulates HIF-1α IRES-mediated translation during hypoxia

(2005) NUCLEIC ACIDS RESEARCH. 33(21). p.6884-6894
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Abstract
When oxygen supply is restricted, protein synthesis is rapidly abrogated owing to inhibition of global translation. However, HIF-1 alpha protein expression can persist during hypoxia, owing to an internal ribosome entry site (IRES) in the 5'-untranslated region of its mRNA. Here, we report on the molecular mechanism of HIF-1 alpha IRES-mediated translation during oxygen deprivation. Using RNA affinity chromatography and UV-crosslinking experiments, we show that the polypyrimidine tract binding protein (PTB) can specifically interact with the HIF-1 alpha IRES, and that this interaction is enhanced in hypoxic conditions. Overexpression of PTB enhanced HIF-1 alpha IRES activity, whereas RNA interference-mediated downregulation of PTB protein expression inhibited HIF-1 alpha IRES activity. Furthermore, hypoxia-induced stimulation of the HIF-1 alpha IRES was reduced in cells in which PTB function was downregulated. In agreement with these results, the IRES activity of HIF-1 alpha IRES deletion mutants that are deficient in PTB-binding could not be stimulated by oxygen deprivation. All together, our data suggest that PTB plays a stimulatory role in the IRES-mediated translation of HIF-1 alpha when oxygen supply is limited.
Keywords
INDUCIBLE FACTOR 1-ALPHA, INTERNAL RIBOSOME ENTRY, FACTOR MESSENGER-RNA, VIRUS-RNA, ALTERNATIVE TRANSLATION, EFFICIENT TRANSLATION, INITIATION-FACTOR, IN-VITRO, N-RAS, SITE

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Citation

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MLA
Schepens, Bert, Sandrine Tinton, Yanik Bruynooghe, et al. “The Polypyrimidine Tract-binding Protein Stimulates HIF-1α IRES-mediated Translation During Hypoxia.” NUCLEIC ACIDS RESEARCH 33.21 (2005): 6884–6894. Print.
APA
Schepens, B., Tinton, S., Bruynooghe, Y., Beyaert, R., & Cornelis, S. (2005). The polypyrimidine tract-binding protein stimulates HIF-1α IRES-mediated translation during hypoxia. NUCLEIC ACIDS RESEARCH, 33(21), 6884–6894.
Chicago author-date
Schepens, Bert, Sandrine Tinton, Yanik Bruynooghe, Rudi Beyaert, and Sigrid Cornelis. 2005. “The Polypyrimidine Tract-binding Protein Stimulates HIF-1α IRES-mediated Translation During Hypoxia.” Nucleic Acids Research 33 (21): 6884–6894.
Chicago author-date (all authors)
Schepens, Bert, Sandrine Tinton, Yanik Bruynooghe, Rudi Beyaert, and Sigrid Cornelis. 2005. “The Polypyrimidine Tract-binding Protein Stimulates HIF-1α IRES-mediated Translation During Hypoxia.” Nucleic Acids Research 33 (21): 6884–6894.
Vancouver
1.
Schepens B, Tinton S, Bruynooghe Y, Beyaert R, Cornelis S. The polypyrimidine tract-binding protein stimulates HIF-1α IRES-mediated translation during hypoxia. NUCLEIC ACIDS RESEARCH. 2005;33(21):6884–94.
IEEE
[1]
B. Schepens, S. Tinton, Y. Bruynooghe, R. Beyaert, and S. Cornelis, “The polypyrimidine tract-binding protein stimulates HIF-1α IRES-mediated translation during hypoxia,” NUCLEIC ACIDS RESEARCH, vol. 33, no. 21, pp. 6884–6894, 2005.
@article{325305,
  abstract     = {When oxygen supply is restricted, protein synthesis is rapidly abrogated owing to inhibition of global translation. However, HIF-1 alpha protein expression can persist during hypoxia, owing to an internal ribosome entry site (IRES) in the 5'-untranslated region of its mRNA. Here, we report on the molecular mechanism of HIF-1 alpha IRES-mediated translation during oxygen deprivation. Using RNA affinity chromatography and UV-crosslinking experiments, we show that the polypyrimidine tract binding protein (PTB) can specifically interact with the HIF-1 alpha IRES, and that this interaction is enhanced in hypoxic conditions. Overexpression of PTB enhanced HIF-1 alpha IRES activity, whereas RNA interference-mediated downregulation of PTB protein expression inhibited HIF-1 alpha IRES activity. Furthermore, hypoxia-induced stimulation of the HIF-1 alpha IRES was reduced in cells in which PTB function was downregulated. In agreement with these results, the IRES activity of HIF-1 alpha IRES deletion mutants that are deficient in PTB-binding could not be stimulated by oxygen deprivation. All together, our data suggest that PTB plays a stimulatory role in the IRES-mediated translation of HIF-1 alpha when oxygen supply is limited.},
  author       = {Schepens, Bert and Tinton, Sandrine and Bruynooghe, Yanik and Beyaert, Rudi and Cornelis, Sigrid},
  issn         = {0305-1048},
  journal      = {NUCLEIC ACIDS RESEARCH},
  keywords     = {INDUCIBLE FACTOR 1-ALPHA,INTERNAL RIBOSOME ENTRY,FACTOR MESSENGER-RNA,VIRUS-RNA,ALTERNATIVE TRANSLATION,EFFICIENT TRANSLATION,INITIATION-FACTOR,IN-VITRO,N-RAS,SITE},
  language     = {eng},
  number       = {21},
  pages        = {6884--6894},
  title        = {The polypyrimidine tract-binding protein stimulates HIF-1α IRES-mediated translation during hypoxia},
  url          = {http://dx.doi.org/10.1093/nar/gki1000},
  volume       = {33},
  year         = {2005},
}

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