Premium
Translation of heat shock proteins is regulated by poly(A)‐binding protein assembly
Author(s) -
Katanski Christopher D,
Riback Joshua,
Pilipenko Evgeny,
Drummond David Allan
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.763.10
Subject(s) - poly(a) binding protein , heat shock protein , microbiology and biotechnology , messenger rna , five prime untranslated region , transcription (linguistics) , untranslated region , protein biosynthesis , rna binding protein , translation (biology) , hspa4 , chemistry , hspa14 , stress granule , gene , biology , hsp70 , biochemistry , linguistics , philosophy
How do cells sense and respond to changes in the environment? During heat stress, numerous eukaryotic RNA and protein species assemble into macromolecular bodies ‐ stress granules ‐ the function of which is largely unknown. Simultaneously, cells increase transcription of genes encoding heat shock proteins, many of which are molecular chaperones. In addition to increased transcription, the mRNA for these genes is also translated more efficiently. Thus, heat shock protein production is regulated by both transcription and translation. These heat‐induced mRNAs have exceptionally A‐rich 5′ untranslated regions (UTRs), which have long been known to mediate cap‐independent translation. We observe that poly(A)‐binding protein (PABP, Pab1 in S. cerevisiae) is bound to these A‐rich UTRs during exponential growth. Pab1 is able to repress translation of its own mRNA by binding a similar A‐rich UTR. We find that Pab1 represses translation of mRNA by binding A‐rich UTRs of heat shock proteins. Further, we propose that during heat‐shock, as Pab1 assembles into heat‐induced RNA‐protein granules, Pab1 releases bound 5′ UTRs, and relieves repression. We have recapitulated Pab1‐mediated repression and heat‐induced relief with an in vitro translation system. Moreover, yeast expressing assembly‐impaired Pab1 are not able to grow at elevated temperature; this result is consistent with disruption of an assembly‐mediated regulatory mechanism. Viewed through this lens, formation of RNA‐protein granules is a regulatory response, whose functions include translational regulation. Support or Funding Information The molecular and cellular biology training grant T32 GM007183