title: Cap-independent protein synthesis is enhanced by betaine under hypertonic conditions.
abstract: Protein synthesis is one of the main cellular functions inhibited during hypertonic challenge. The subsequent accumulation of the compatible osmolyte betaine during the later adaptive response allows not only recovery of translation but also its stimulation. In this paper, we show that betaine modulates translation by enhancing the formation of cap-independent 48 S pre-initiation complexes, leaving cap-dependent 48 S pre-initiation complexes basically unchanged. In the presence of betaine, CrPV IRES- and sodium-dependent neutral amino acid transporter-2 (SNAT2) 5'-UTR-driven translation is 2- and 1.5-fold stimulated in MCF7 cells, respectively. Thus, betaine could provide an advantage in translation of messengers coding for proteins implicated in the response of cells to different stressors, which are often recognized by ribosomal 40 S subunit through simplified cap-independent mechanisms.
authors.affiliation: Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Carnicelli
authors.affiliation: Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Arfilli
authors.affiliation: Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Onofrillo
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Università di Parma, Parma, Italy.
authors.forename: Roberta R
authors.initials: RR
authors.lastname: Alfieri
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Università di Parma, Parma, Italy.
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Petronini
authors.affiliation: Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Montanaro
authors.affiliation: Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy. Electronic address: maurizio.brigotti@unibo.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Brigotti
mesh_terms: D020121:5' Untranslated Regions; D026924:Amino Acid Transport System A / Q000378:metabolism; D000818:Animals; D001622:Betaine / Q000378:metabolism* / Q000494:pharmacology*; D002474:Cell-Free System; D006801:Humans; D006982:Hypertonic Solutions; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D009997:Osmotic Pressure; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000235:genetics; D012315:RNA Caps / Q000378:metabolism*; D011817:Rabbits; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D026924:Amino Acid Transport System A; D006982:Hypertonic Solutions; D012315:RNA Caps; C498797:SLC38A2 protein, human; D001622:Betaine; D008156:Luciferases
keywords: 48 S pre-initiation complex; 5′ untranslated region; Betaine; Compatible osmolytes; Hyperosmolarity; Protein synthesis