title: Mammalian Hsp70 and Hsp110 proteins bind to RNA motifs involved in mRNA stability.
abstract: In this study, in vitro RNA binding by members of the mammalian 70-kDa heat shock protein (Hsp) family was examined. We show that Hsp/Hsc70 and Hsp110 proteins preferentially bound AU-rich RNA in vitro. Inhibition of RNA binding by ATP suggested the involvement of the N-terminal ATP-binding domain. By using deletion mutants of Hsp110 protein, a diverged Hsp70 family member, RNA binding was localized to the N-terminal ATP-binding domain of the molecule. The C-terminal peptide-binding domain did not bind RNA, but its engagement by a peptide substrate abrogated RNA binding by the N terminus of the protein. Interestingly, removal of the C-terminal alpha-helical structure or the alpha-loop domain unique to Hsp110 immediately downstream of the peptide-binding domain, but not both, resulted in considerably increased RNA binding as compared with the wild type protein. Finally, a 70-kDa activity was immunoprecipitated from RNA-protein complexes formed in vitro between cytoplasmic proteins of human lymphocytes and AU-rich RNA. These findings support the idea that certain heat shock proteins may act as RNA-binding entities in vivo to guide the appropriate folding of RNA substrates for subsequent regulatory processes such as mRNA degradation and/or translation.
authors.affiliation: Department of Medical Microbiology and Immunology, University Medical School of Pécs, H-7643 Pécs, Hungary. THenics@intercell.co.at
authors.forename: T
authors.initials: T
authors.lastname: Henics
authors.forename: E
authors.initials: E
authors.lastname: Nagy
authors.forename: H J
authors.initials: HJ
authors.lastname: Oh
authors.forename: P
authors.initials: P
authors.lastname: Csermely
authors.forename: A
authors.initials: A
authors.lastname: von Gabain
authors.forename: J R
authors.initials: JR
authors.lastname: Subjeck
mesh_terms: D020413:3' Untranslated Regions; D000255:Adenosine Triphosphate / Q000494:pharmacology; D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D050883:HSC70 Heat-Shock Proteins; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007768:Lactalbumin; D008969:Molecular Sequence Data; D009154:Mutation; D011233:Precipitin Tests; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017384:Sequence Deletion
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000255:Adenosine Triphosphate; D007768:Lactalbumin