title: 5'-Untranslated region of heat shock protein 70 mRNA drives translation under hypertonic conditions.
abstract: In mammalian cells, adaptation to hypertonic conditions leads to the activation of an array of early (cell shrinkage, regulatory volume increase) and late (accumulation of compatible osmolytes) responses and increased level of HSPs (heat shock proteins). Protein synthesis is strongly inhibited few minutes after the hypertonic challenge as demonstrated in whole cells and as reproduced under controlled conditions in cell-free systems. Different mechanisms known to mediate the accumulation of HSP70, such as mRNA transcription and stabilization, require fully active protein synthesis. We show that the 5'-untranslated region of HSP70 messenger drives a hypertonicity-resistant translation (up to 0.425 osmol/kg of water), whereas cap-dependent protein synthesis is almost totally blocked under the same conditions. The results, obtained in cell-free systems and in whole cells, might help to explain why HSP70 is accumulated in cells when total protein synthesis is impaired. We also observed that translation initiated by viral IRES (from Cricket paralysis virus) is highly efficient in cells exposed to hyperosmolarity, suggesting that the resistance to hypertonic conditions is a more general feature of cap-independent translation. The described mechanism may also play a role in the control of translation of other messengers encoding for proteins involved in the adaptation to hypertonicity.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Rocchi
authors.forename: Roberta R
authors.initials: RR
authors.lastname: Alfieri
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Petronini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Montanaro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Brigotti
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D002474:Cell-Free System; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D009997:Osmotic Pressure; D014176:Protein Biosynthesis; D011817:Rabbits; D012462:Saline Solution, Hypertonic
chemical_list: D020121:5' Untranslated Regions; D018840:HSP70 Heat-Shock Proteins; D012462:Saline Solution, Hypertonic