title: 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.
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.
authors.affiliation: Department of Nutrition, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4954, USA.
authors.forename: Mithu
authors.initials: M
authors.lastname: Majumder
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yaman
authors.forename: Francesca
authors.initials: F
authors.lastname: Gaccioli
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Zeenko
authors.forename: Chuanping
authors.initials: C
authors.lastname: Wang
authors.forename: Mark G
authors.initials: MG
authors.lastname: Caprara
authors.forename: Richard C
authors.initials: RC
authors.lastname: Venema
authors.forename: Anton A
authors.initials: AA
authors.lastname: Komar
authors.forename: Martin D
authors.initials: MD
authors.lastname: Snider
authors.forename: Maria
authors.initials: M
authors.lastname: Hatzoglou
mesh_terms: D020121:5' Untranslated Regions; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D027201:Cationic Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation; D034664:Heterogeneous-Nuclear Ribonucleoprotein L / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009690:Nucleic Acid Conformation; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D000596:Amino Acids; D027201:Cationic Amino Acid Transporter 1; D034664:Heterogeneous-Nuclear Ribonucleoprotein L; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D038941:Polypyrimidine Tract-Binding Protein