RGD Reference Report - 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.

General

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.
Authors:	Majumder, M Yaman, I Gaccioli, F Zeenko, VV Wang, C Caprara, MG Venema, RC Komar, AA Snider, MD Hatzoglou, M
Citation:	Majumder M, etal., Mol Cell Biol. 2009 May;29(10):2899-912. doi: 10.1128/MCB.01774-08. Epub 2009 Mar 9.
RGD ID:	9999430
Pubmed:	PMID:19273590 (View Abstract at PubMed)
PMCID:	PMC2682027 (View Article at PubMed Central)
DOI:	DOI:10.1128/MCB.01774-08 (Journal Full-text)
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.

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
cellular response to amino acid starvation		IDA		9999430		RGD
positive regulation of mRNA binding		IMP		9999430		RGD
positive regulation of translation		IMP		9999430; 9999430		RGD

Molecular Function

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
mRNA binding		IDA		9999430		RGD

Objects Annotated

Genes (Rattus norvegicus)

Hnrnpl (heterogeneous nuclear ribonucleoprotein L)

Ptbp1 (polypyrimidine tract binding protein 1)

Additional Information

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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.