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PMID: 27105849 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Do nucleic acids moonlight as molecular chaperones?

Nucleic acids research ·Vol. 44 ·No. 10 ·2016-00-02 ·Pages 4835-45

Docter BE, Horowitz S, Gray MJ, Jakob U, Bardwell JC

Abstract

Organisms use molecular chaperones to combat the unfolding and aggregation of proteins. While protein chaperones have been widely studied, here we demonstrate that DNA and RNA exhibit potent chaperone activity in vitro Nucleic acids suppress the aggregation of classic chaperone substrates up to 300-fold more effectively than the protein chaperone GroEL. Additionally, RNA cooperates with the DnaK chaperone system to refold purified luciferase. Our findings reveal a possible new role for nucleic acids within the cell: that nucleic acids directly participate in maintaining proteostasis by preventing protein aggregation.

MeSH Terms
Chaperonin 60/metabolism DNA/metabolism Molecular Chaperones/metabolism Protein Aggregates Protein Denaturation Protein Refolding RNA/metabolism
Chemicals
Chaperonin 60 Molecular Chaperones Protein Aggregates RNA DNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Docter Brianne E ORCID
Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI 48109, USA.
Horowitz Scott
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Gray Michael J
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Jakob Ursula
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Bardwell James C A
Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI 48109, USA Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA jbardwel@umich.edu.
References (52)
52 references, click to expand
  1. Accurate secondary structure prediction and fold recognition for circular dichroism spectroscopy.
    Proc Natl Acad Sci U S A. 2015 Jun 16;112(24):E3095-103 PMID: 26038575
  2. Bile salts act as effective protein-unfolding agents and instigators of disulfide stress in vivo.
    Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):E1610-9 PMID: 24706920
  3. Chemical and pharmacological chaperones: application for recombinant protein production and protein folding diseases.
    Curr Med Chem. 2011;18(1):1-15 PMID: 21110818
  4. Reconstitution of a heat shock effect in vitro: influence of GroE on the thermal aggregation of alpha-glucosidase from yeast.
    Biochemistry. 1991 Dec 17;30(50):11609-14 PMID: 1751484
  5. Protein folding activity of the ribosome (PFAR) -- a target for antiprion compounds.
    Viruses. 2014 Oct 23;6(10):3907-24 PMID: 25341659
  6. The complete genome sequence of Escherichia coli K-12.
    Science. 1997 Sep 5;277(5331):1453-62 PMID: 9278503
  7. Polyphosphate is a primordial chaperone.
    Mol Cell. 2014 Mar 6;53(5):689-99 PMID: 24560923
  8. Inhibition of TDP-43 aggregation by nucleic acid binding.
    PLoS One. 2013 May 30;8(5):e64002 PMID: 23737961
  9. Ribosome-DnaK interactions in relation to protein folding.
    Mol Microbiol. 2003 Jun;48(6):1679-92 PMID: 12791147
  10. The ribosome can prevent aggregation of partially folded protein intermediates: studies using the Escherichia coli ribosome.
    PLoS One. 2014 May 07;9(5):e96425 PMID: 24805251
  11. Free mRNA in excess upon polysome dissociation is a scaffold for protein multimerization to form stress granules.
    Nucleic Acids Res. 2014 Jul;42(13):8678-91 PMID: 25013173
  12. Stress granules: the Tao of RNA triage.
    Trends Biochem Sci. 2008 Mar;33(3):141-50 PMID: 18291657
  13. Translationally repressed mRNA transiently cycles through stress granules during stress.
    Mol Biol Cell. 2008 Oct;19(10):4469-79 PMID: 18632980
  14. Limiting laws and counterion condensation in polyelectrolyte solutions. IV. The approach to the limit and the extraordinary stability of the charge fraction.
    Biophys Chem. 1977 Sep;7(2):95-102 PMID: 901909
  15. Polymerization of murine recombinant prion protein in nucleic acid solution.
    Arch Virol. 1999;144(9):1751-63 PMID: 10542024
  16. Protein folding by domain V of Escherichia coli 23S rRNA: specificity of RNA-protein interactions.
    J Bacteriol. 2008 May;190(9):3344-52 PMID: 18310328
  17. Binding with nucleic acids or glycosaminoglycans converts soluble protein oligomers to amyloid.
    J Biol Chem. 2012 Jan 2;287(1):736-47 PMID: 22102410
  18. Influence of molecular and chemical chaperones on protein folding.
    Cell Stress Chaperones. 1996 Jun;1(2):109-15 PMID: 9222596
  19. Another function for the mitochondrial ribosomal RNA: protein folding.
    Biochemistry. 2001 Sep 25;40(38):11559-64 PMID: 11560505
  20. Activation of the redox-regulated molecular chaperone Hsp33--a two-step mechanism.
    Structure. 2001 May 9;9(5):377-87 PMID: 11377198
  21. Small heat shock proteins are molecular chaperones.
    J Biol Chem. 1993 Jan 25;268(3):1517-20 PMID: 8093612
  22. RNA-mediated chaperone type for de novo protein folding.
    RNA Biol. 2009 Jan-Mar;6(1):21-4 PMID: 19106620
  23. GroE facilitates refolding of citrate synthase by suppressing aggregation.
    Biochemistry. 1991 Feb 12;30(6):1586-91 PMID: 1671555
  24. Trigger Factor and DnaK possess overlapping substrate pools and binding specificities.
    Mol Microbiol. 2003 Mar;47(5):1317-28 PMID: 12603737
  25. Identification of a redox-regulated chaperone network.
    EMBO J. 2004 Jan 14;23(1):160-8 PMID: 14685279
  26. NemR is a bleach-sensing transcription factor.
    J Biol Chem. 2013 May 10;288(19):13789-98 PMID: 23536188
  27. Stress granules.
    Curr Biol. 2009 May 26;19(10):R397-8 PMID: 19467203
  28. Impact of P-Site tRNA and antibiotics on ribosome mediated protein folding: studies using the Escherichia coli ribosome.
    PLoS One. 2014 Jul 07;9(7):e101293 PMID: 25000563
  29. DNA converts cellular prion protein into the beta-sheet conformation and inhibits prion peptide aggregation.
    J Biol Chem. 2001 Dec 28;276(52):49400-9 PMID: 11604397
  30. Stress granules are dispensable for mRNA stabilization during cellular stress.
    Nucleic Acids Res. 2015 Feb 27;43(4):e26 PMID: 25488811
  31. Purification and concentration of DNA from aqueous solutions.
    Curr Protoc Mol Biol. 2002 Aug;Chapter 2:Unit 2.1A PMID: 18265306
  32. DNA induced folding/fibrillation of alpha-synuclein: new insights in Parkinson's disease.
    Front Biosci (Landmark Ed). 2010 Jan 01;15:418-36 PMID: 20036828
  33. Some like it hot: the structure and function of small heat-shock proteins.
    Nat Struct Mol Biol. 2005 Oct;12(10):842-6 PMID: 16205709
  34. Hsp90 chaperones protein folding in vitro.
    Nature. 1992 Jul 9;358(6382):169-70 PMID: 1614549
  35. Quantitative determination of protein stability and ligand binding by pulse proteolysis.
    Curr Protoc Protein Sci. 2006 Dec;Chapter 20:Unit 20.11 PMID: 18429306
  36. Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter.
    J Bacteriol. 1995 Jul;177(14):4121-30 PMID: 7608087
  37. Nucleic acid aptamers as stabilizers of proteins: the stability of tetanus toxoid.
    Pharm Res. 2013 Jul;30(7):1871-82 PMID: 23568526
  38. Acceleration of the refolding of Arc repressor by nucleic acids and other polyanions.
    Nat Struct Biol. 1999 Jun;6(6):569-73 PMID: 10360363
  39. Identification of thermolabile Escherichia coli proteins: prevention and reversion of aggregation by DnaK and ClpB.
    EMBO J. 1999 Dec 15;18(24):6934-49 PMID: 10601016
  40. Reversible, Specific, Active Aggregates of Endogenous Proteins Assemble upon Heat Stress.
    Cell. 2015 Sep 10;162(6):1286-98 PMID: 26359986
  41. Protein folding in vivo revisited.
    Curr Protein Pept Sci. 2013 Dec;14(8):721-33 PMID: 24384034
  42. Protein solubility and folding enhancement by interaction with RNA.
    PLoS One. 2008 Jul 16;3(7):e2677 PMID: 18628952
  43. RNA molecules stimulate prion protein conversion.
    Nature. 2003 Oct 16;425(6959):717-20 PMID: 14562104
  44. Substrate recognition by the AAA+ chaperone ClpB.
    Nat Struct Mol Biol. 2004 Jul;11(7):607-15 PMID: 15208691
  45. The various facets of the protein-folding activity of the ribosome.
    Biotechnol J. 2011 Jun;6(6):668-73 PMID: 21567961
  46. Ligand-binding interactions and stability.
    Methods Mol Biol. 2009;490:135-64 PMID: 19157082
  47. RNA granules: post-transcriptional and epigenetic modulators of gene expression.
    Nat Rev Mol Cell Biol. 2009 Jun;10(6):430-6 PMID: 19461665
  48. Nucleic acid induced unfolding of recombinant prion protein globular fragment is pH dependent.
    Protein Sci. 2014 Dec;23(12):1780-8 PMID: 25271002
  49. Chaperone activity with a redox switch.
    Cell. 1999 Feb 5;96(3):341-52 PMID: 10025400
  50. ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure.
    Cell. 2016 Jan 28;164(3):487-98 PMID: 26777405
  51. Protein folding on the ribosome.
    Curr Opin Struct Biol. 2010 Feb;20(1):33-45 PMID: 20149635
  52. Reactivation of denatured proteins by 23S ribosomal RNA: role of domain V.
    Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8284-7 PMID: 8710862
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
Published
2016-00-02
Epub
2016-00-21
Pages
4835-45
Language
English
Region
England
NLM ID
0411011
PMCID
PMC4889950
Subset
IM
Grants
NIGMS NIH HHS · R01 GM102829 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R01 GM065318 · United States
NIGMS NIH HHS · R01 GM116582 · United States
NIGMS NIH HHS · T32 GM007315 · United States
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