The hnRNA-binding proteins hnRNP L and PTB are required for efficient translation of the Cat-1 arginine/lysine transporter mRNA during amino acid starvation

Mithu Majumder, Ibrahim Yaman, Francesca Gaccioli, Vladimir V. Zeenko, Chuanping Wang, Mark G. Caprara, Richard C Venema, Anton A. Komar, Martin D. Snider, Maria Hatzoglou

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

The response to amino acid starvation involves the global decrease of protein synthesis and an increase in the translation of some mRNAs that contain an internal ribosome entry site (IRES). It was previously shown that translation of the mRNA for the arginine/lysine amino acid transporter Cat-1 increases during amino acid starvation via a mechanism that utilizes an IRES in the 5′ untranslated region of the Cat-1 mRNA. It is shown here that polypyrimidine tract binding protein (PTB) and an hnRNA binding protein, heterogeneous nuclear ribonucleoprotein L (hnRNP L), promote the efficient translation of Cat-1 mRNA during amino acid starvation. Association of both proteins with Cat-1 mRNA increased during starvation with kinetics that paralleled that of IRES activation, although the levels and subcellular distribution of the proteins were unchanged. The sequence CUUUCU within the Cat-1 IRES was important for PTB binding and for the induction of translation during amino acid starvation. Binding of hnRNP L to the IRES or the Cat-1 mRNA in vivo was independent of PTB binding but was not sufficient to increase IRES activity or Cat-1 mRNA translation during amino acid starvation. In contrast, binding of PTB to the Cat-1 mRNA in vivo required hnRNP L. A wider role of hnRNP L in mRNA translation was suggested by the decrease of global protein synthesis in cells with reduced hnRNP L levels. It is proposed that PTB and hnRNP L are positive regulators of Cat-1 mRNA translation via the IRES under stress conditions that cause a global decrease of protein synthesis.

Original languageEnglish (US)
Pages (from-to)2899-2912
Number of pages14
JournalMolecular and Cellular Biology
Volume29
Issue number10
DOIs
StatePublished - May 1 2009

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Heterogeneous-Nuclear Ribonucleoprotein L
Polypyrimidine Tract-Binding Protein
Starvation
Lysine
Arginine
Carrier Proteins
Cats
Amino Acids
Messenger RNA
Protein Biosynthesis
Protein Binding
Proteins
Amino Acid Transport Systems
5' Untranslated Regions
Internal Ribosome Entry Sites

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

The hnRNA-binding proteins hnRNP L and PTB are required for efficient translation of the Cat-1 arginine/lysine transporter mRNA during amino acid starvation. / Majumder, Mithu; Yaman, Ibrahim; Gaccioli, Francesca; Zeenko, Vladimir V.; Wang, Chuanping; Caprara, Mark G.; Venema, Richard C; Komar, Anton A.; Snider, Martin D.; Hatzoglou, Maria.

In: Molecular and Cellular Biology, Vol. 29, No. 10, 01.05.2009, p. 2899-2912.

Research output: Contribution to journalArticle

Majumder, M, Yaman, I, Gaccioli, F, Zeenko, VV, Wang, C, Caprara, MG, Venema, RC, Komar, AA, Snider, MD & Hatzoglou, M 2009, 'The hnRNA-binding proteins hnRNP L and PTB are required for efficient translation of the Cat-1 arginine/lysine transporter mRNA during amino acid starvation', Molecular and Cellular Biology, vol. 29, no. 10, pp. 2899-2912. https://doi.org/10.1128/MCB.01774-08
Majumder, Mithu ; Yaman, Ibrahim ; Gaccioli, Francesca ; Zeenko, Vladimir V. ; Wang, Chuanping ; Caprara, Mark G. ; Venema, Richard C ; Komar, Anton A. ; Snider, Martin D. ; Hatzoglou, Maria. / The hnRNA-binding proteins hnRNP L and PTB are required for efficient translation of the Cat-1 arginine/lysine transporter mRNA during amino acid starvation. In: Molecular and Cellular Biology. 2009 ; Vol. 29, No. 10. pp. 2899-2912.
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AU - Zeenko, Vladimir V.

AU - Wang, Chuanping

AU - Caprara, Mark G.

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