title: Widespread regulation of translation by elongation pausing in heat shock.
abstract: Global repression of protein synthesis is a hallmark of the cellular stress response and has been attributed primarily to inhibition of translation initiation, although this mechanism may not always explain the full extent of repression. Here, using ribosome footprinting, we show that 2 hr of severe heat stress triggers global pausing of translation elongation at around codon 65 on most mRNAs in both mouse and human cells. The genome-wide nature of the phenomenon, its location, and features of protein N termini suggested the involvement of ribosome-associated chaperones. After severe heat shock, Hsp70's interactions with the translational machinery were markedly altered and its association with ribosomes was reduced. Pretreatment with mild heat stress or overexpression of Hsp70 protected cells from heat shock-induced elongation pausing, while inhibition of Hsp70 activity triggered elongation pausing without heat stress. Our findings suggest that regulation of translation elongation in general, and by chaperones in particular, represents a major component of cellular stress responses.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors.forename: Reut
authors.initials: R
authors.lastname: Shalgi
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Hurt
authors.forename: Irina
authors.initials: I
authors.lastname: Krykbaeva
authors.forename: Mikko
authors.initials: M
authors.lastname: Taipale
authors.forename: Susan
authors.initials: S
authors.lastname: Lindquist
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Burge
mesh_terms: D016475:3T3 Cells; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics; D006801:Humans; D051379:Mice; D008954:Models, Biological; D016366:Open Reading Frames / Q000235:genetics; D010441:Peptide Chain Elongation, Translational; D011132:Polyribosomes / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D060066:Protein Interaction Maps / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D000596:Amino Acids; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger