Skip to main content

RNA Binding by Members of the 70-kDa Family of Molecular Chaperones

  • Chapter
RNA Binding Proteins

Part of the book series: Endocrine Updates ((ENDO,volume 16))

  • 246 Accesses

Abstract

Research on heat shock and other stress proteins (hsps) has revealed a number of intriguing aspects about this remarkable class of molecules. First, hsps are highly abundant proteins in cells even under non-stress conditions. This abundance holds for virtually all organisms or cell types examined. Second, hsps are the most phylogenetically conserved proteins known to biology with an overall primary amino acid sequence homology of some 50 % between Escherichia coli and man. Third, hsps have been implicated in a myriad of cellular processes throughout the years. Although the majority of these biological functions delineate hsps as molecular chaperones, recent evidence suggests that certain heat shock proteins possess a likely ancient, evolutionarily conserved role pointing beyond their classical chaperoning function. This chapter deals with a recently described novel feature of the mammalian 70-kDa super-family of molecular chaperones (hsp70, hsc70, hsp110 and grp170), their inherent RATA binding properties. The monograph highlights the RATA sequence preference as well as the RNA-binding domain of these proteins. The influence of ATP and a peptide substrate on RNA-binding —all key components in chaperoning function- will also be detailed. Although the data were obtained using both hsp/hsc70 and hsp110 as the RATA binding partner, since most of the supporting evidence deals with hsp70/hsc70, discussions of possible in vivo functions will mainly be extended to these widely characterized stress proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Glick, B. S. (1995) Can Hsp70 proteins act as force-generating motors? Cell, 80: 11–14.

    Article  PubMed  CAS  Google Scholar 

  2. Craig, E. A., Gambill, B. D., and Nelson, R. J. (1993) Heat shock proteins: molecular chaperones of protein biogenesis. Microbiol. Rev., 57: 402–414.

    PubMed  CAS  Google Scholar 

  3. Rutherford, S. L., and Zuker, C. S. Protein folding and the regulation of signaling pathways. (1994) Cell, 79: 1129–1132.

    Article  PubMed  CAS  Google Scholar 

  4. Bukau, B., and Horwich, A. L. (1998) The Hsp70 and Hsp60 chaperone machines. Cell, 92: 351–366.

    Article  PubMed  CAS  Google Scholar 

  5. Hart!, F. U. (1996) Molecular chaperones in cellular protein folding. Nature, 381: 571–579.

    Article  Google Scholar 

  6. Johnson, J. L., and Craig, E. A. (1997) Protein folding in vivo: unraveling complex pathways. Cell, 90: 201–204.

    Article  PubMed  CAS  Google Scholar 

  7. Lee-Yoon, D., Easton, D., Murawski, M., Burd, R. and Subjeck, J. R. (1995) Identification of a major subfamily of large hsp70-like proteins through the cloning of the mammalian 110-kDa heat shock protein. J. Biol. Chem., 270: 15725–15733.

    Article  PubMed  CAS  Google Scholar 

  8. Easton, D.P., Kaneko, Y. and Subjeck, J.R. The hsp110 and grp170 stress proteins: Newly recognized relatives of the hsp70s. Cell Stress and Chaperones,in press.

    Google Scholar 

  9. Zhu, X., Zhao, X., Burkholder, W. F., Gragerov, A., Ogata, C. M., Gottesman, M. E. and Hendrickson, W. A. (1996) Structural analysis of substrate binding by the molecular chaperone DnaK. Science, 272: 1606–1614.

    Article  PubMed  CAS  Google Scholar 

  10. Oh, H.J., Easton, D.P., Murawski, M. Kaneko, Y. and Subjeck, J.R. The chaperoning activity of hsp110: Identification of functional domains by use of targeted deletions. J. Biol. Chem., 274: 15712–15718.

    Google Scholar 

  11. Oh, H. J., Chen, X. and Subjeck, J. R. (1997) hsp110 protects heat-denatured proteins and confers cellular thermoresistance. J. Biol. Chem., 272: 31636–31640.

    Google Scholar 

  12. Chen, X., Easton, D., Oh, H. J., Lee-Yoon, D., Liu, X. and Subjeck, J. (1996) The 170 kDa glucose regulated stress protein is a large HSP70-, HSP110-like protein of the endoplasmic reticulum. FEBS Lett., 380: 68–72.

    Article  PubMed  CAS  Google Scholar 

  13. Ruggero, D., Ciammaruconi, A. and Londei, P. (1998) The chaperonin of the archaeon, Sulfolobus solfataricus is an RNA-binding protein that participates in ribosomal RNA processing. EMBO J., 17: 3471–3477.

    Article  PubMed  CAS  Google Scholar 

  14. Török, Zs., Horvath, I., Goloubinoff, P., Kovacs, E., Glatz. A., Balogh, G. and VIgh, L. (1997) Evidence for a lipochaperonin: association of active protein-folding GroESL oligomers with lipids can stabilize membranes under heat shock conditions. Proc. Natl. Acad. Sci. USA, 94: 2192–2197.

    Google Scholar 

  15. Wells, D. R., Tanguay, R. L., Le, H. and Gallie, D. R. (1998) Hsp101 functions as a specific translational regulatory protein whose activity is regulated by nutrient status. Genes Develop., 12: 3236–3251.

    Article  PubMed  CAS  Google Scholar 

  16. Sohlberg, B., Lundberg, U., Hartl, F-U. and von Gabain, A. (1993) Functional interaction of heat shock protein GroEL with an RNase E-like activity in Escherichia coli. Proc. Natl. Acad. Sci. USA, 90: 277–281.

    Article  CAS  Google Scholar 

  17. Georgellis, D., Sohlberg, B., Hartl, F-U. and von Gabain, A. (1995) Identification of GroEL as a constituent of an mRNA-protection complex in Escherichia coli. Molec. Microbiol., 16: 1259–1268.

    Article  CAS  Google Scholar 

  18. Miczak, A., Kaberdin, V. R., Wei, C-L. and Lin-Chao, S. (1996) Proteins associated with Rnase E in a multicomponent ribonucleolytic complex. Proc. Natl. Acad. Sci. USA, 93: 3865–3869.

    Article  CAS  Google Scholar 

  19. DiDomenico, B. J., Bugaisky, G. E. and Lindquist, S. (1982) The heat shock response is self-regulated at both the transcriptional and posttranscriptional levels. Cell, 31: 593603.

    Google Scholar 

  20. Simcox, A. A., Cheney, C. M., Hoffman, E. P. and Shearn, A. (1985) A deletion of the 3’ end of the Drosophila melanogaster hsp70 gene increases stability of mutant mRNA during recovery from heat shock. Mol. Cell. Biol., 5: 3397–3402.

    PubMed  CAS  Google Scholar 

  21. Theodorakis, N. G. and Morimoto, R. (1987) Posttranscriptional regulation of hsp70 expression in human cells: Effects of heat shock, inhibition of protein synthesis, and adenovirus infection on translation and mRNA stability. Mol. Cell. Biol., 7: 4357–4368.

    PubMed  CAS  Google Scholar 

  22. Yost, H. J., Petersen, R. B. and Lindquist, S. (1990) Posttranscriptional regulation of heat shock protein synthesis in Drosophila. In: Stress proteins in biology and medicine. Ed by D. Pauli and A. Tissières. pp 379–409.

    Google Scholar 

  23. Wilhelm, M. L., Reinholt, J., Gangloff, J., Dirheimer, G. and Wilhelm, F. X. (1994) Transfer RNA binding protein in the nucleus of Saccharomyces cerevisiae. FEBS Lett., 349: 260–264.

    Article  CAS  Google Scholar 

  24. Scandurro, A. B., Rondon, I. J., Wilson, R. B., Tenenbaum, S. A., Garry, R. and Beckman, B. (1997) Interaction of erythropoetin RNA binding protein with erythropoetin RNA requires an association with heat shock protein 70. Kidney Internatl., 51: 579–584.

    Article  CAS  Google Scholar 

  25. Laroia, G., Cuesta, R., Brewer, G. and Schneider, R. J. (1999) Control of mRNA decay by heat shock-ubiquitin-degradosome pathway. Science, 284: 499–502.

    Article  PubMed  CAS  Google Scholar 

  26. Malter, J. S. (1989) Identification of an AUUUA-specific messenger RNA binding protein. Science, 246: 664–666.

    Article  PubMed  CAS  Google Scholar 

  27. Henics, T., Sanfridson, A., Hamilton, B. J., Nagy, E. and Rigby, W. F. C. (1994) Enhanced stability of interleukin-2 in MLA 144 cells: Possible role of cytoplasmic AU-rich sequence binding proteins. JBiol. Chem., 269: 5377–5383.

    CAS  Google Scholar 

  28. SoOs, H., Bujaky, Cs., Kiss, A., Kovacs, É., Somoskeöy, Sz. and Henics, T. (1998) Distribution profile and in vivo RNA association of cytoplasmic AU-rich sequence binding proteins in various mammalian cells: effect of the organizational state of cellular architecture. Physiol. Chem. Phys. Med. NMR., 30: 163–174.

    PubMed  CAS  Google Scholar 

  29. Henics, T., Nagy, E., Oh, H. J., Csermely, P., von Gabain, A. and Subjeck, J. R. (1999) Mammalian Hsp70 and Hsp110 proteins bind to RNA motifs involved in mRNA stability. JBiol. Chem., 274: 17318–17324.

    Article  CAS  Google Scholar 

  30. Chen, C.-Y. A. and Shyu, A.-B. (1995) AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem. Sci., 20: 465–470.

    Article  PubMed  CAS  Google Scholar 

  31. a. Zimmer, C., von Gabain, A. and Henics, T. (2001) Analysis of sequence-specific binding of RNA to Hsp70 and its various homologues indicates the involvement of Nand C-terminal interactions. RNA, in press.

    Google Scholar 

  32. Nagy, E., Henics, T., Eckert, M., Miseta, A., Lightowlers, R. N. and Kellermayer, M. (2000) Identification of the NAD+-binding fold of glyceraldehyde-3-phosphate dehydrogenase as a novel RNA-binding domain. Biochem Biophys Res Commun., 275: 253–260.

    Article  PubMed  CAS  Google Scholar 

  33. Liberek, K., Skowyra, D., Zylicz, M., Johnson, C. and Georgopoulos, C. (1991) The Escherichia coli DnaK chaperone, the 70-kDa heat shock protein eukaryotic equivalent, changes conformation upon ATP hydrolysis, thus triggering its dissociation from a bound target protein. JBiol. Chem., 266: 14491–14496.

    CAS  Google Scholar 

  34. Buchberger, A., Theyssen, H., Schröder, H., McCarty, J. S., Virgallita, J., Milkereit, P., Reinstein, J. and Backau, B. (1995) Nucleotide-induced conformational changes in the ATPase and substrate binding domains of the DnaK chaperone provide evidence for interdomain communication. JBiol. Chem., 270: 16903–16910.

    Article  CAS  Google Scholar 

  35. Fung, K. L., Hilgenberg, L., Wang, N. M. and Chirico, W. J. (1996) Conformations of the nucleotide and polypeptide binding domains of a cytosolic Hsp70 molecular chaperone are coupled. J. Biol. Chem., 271: 21559–21565.

    Article  PubMed  CAS  Google Scholar 

  36. James, P., Pfund, C. and Craig, E. A. (1997) Functional specificity among Hsp70 molecular chaperones. Science, 275: 387–389.

    Article  PubMed  CAS  Google Scholar 

  37. Lopez-Buesa, P., Pfund, C. and Craig, E. A. (1998) The biochemical properties of the ATPase activity of a 70-kDa heat shock protein (Hsp70) are governed by the C-terminal domains. Proc. Natl. Acad. Sci. USA, 95: 15253–15258.

    Article  PubMed  CAS  Google Scholar 

  38. Davis, J. E., Voisine, C. and Craig, E. A. (1999) Intragenic suppressors of Hsp70 mutants: Interplay between the ATPase-and peptide-binding domains. Proc. Natl. Acad. Sci. USA, 96: 9269–9276.

    Article  PubMed  CAS  Google Scholar 

  39. Morshauser, R. C., Wang, H., Flynn, G. C. and Zuiderweg, E. R. P. (1995) The peptide-binding domain of the chaperone protein Hsc70 has an unusual secondary structure topology. Biochemistry, 34: 6261–6266.

    Article  PubMed  CAS  Google Scholar 

  40. Sheterline, P., Clayton, J. and Sparrow, J. C. (1996) Actin structure in Actins, 3`d Edition, Academic Press, Ltd. pp 15–51.

    Google Scholar 

  41. Henics, T., Nagy, E. and Szekeres-Barthó, J. (1997) Interaction of AU-rich sequence binding proteins with actin: Possible involvement of the actin-cytoskeleton in lymphokine mRNA turnover. J Cell. Physiol., 173: 19–27.

    Article  PubMed  CAS  Google Scholar 

  42. Nelson, R. J., Ziegelhoffer, T., Nicolet, C., Werner-Washburne, M. and Craig, E. A. (1992) The translation machinery and 70 kd heat shock protein cooperate in protein synthesis. Cell, 71: 97–105.

    Article  PubMed  CAS  Google Scholar 

  43. Pfund, C., Lopez-Hoyo, N., Ziegelhoffer, T., Schilke, B. A., Lopez-Buesa, P., Walter, W. A., Wiedmann, M. and Craig, E. A. (1998) The molecular chaperone Ssb from Saccharomyces cerevisiae is a component of the ribosome-nescent chain complex. EMBO J., 17: 3981–3989.

    Article  PubMed  CAS  Google Scholar 

  44. Beck, S. C. and De Maio, A. (1994) Stabilization of protein synthesis in thermotolerant cells during heat shock. J. Biol. Chem., 269: 21803–21811.

    PubMed  CAS  Google Scholar 

  45. Yan, W., Schilke, B., Pfund, C., Walter, W., Kim, S. and Craig, E. A. (1998) Zuotin, a ribosome-associated DnaJ molecular chaperone. EMBO J., 17: 4809–4817.

    Article  PubMed  CAS  Google Scholar 

  46. Uma, S., Thulasiraman, V. and Matts, R. L. (1999) Dual role for Hsc70 in the biogenesis and regulation of the heme-regulated kinase of the oc subunit of eukaryotic translation initiation factor 2. Mol. Cell. Biol., 19: 5861–5871.

    PubMed  CAS  Google Scholar 

  47. Horton, L.E., James, P., Craig, E.A., and Hensold, J.O. (2001) The yeast hsp70 homologue Ssa is required for translation and interacts with Sisl and Pab1 on translating ribosomes. J Biol Chem 276: 14426–14433.

    PubMed  CAS  Google Scholar 

  48. Wang, X-Y., Chen, X., Oh, H. J., Repsky, E., Kazim, L. and Subjeck, J. (2000) Characterization of native interaction of hsp110 with hsp25 and hsc70. FEBS Lett., 465: 98–102.

    Article  PubMed  CAS  Google Scholar 

  49. Zhang, S., Williams, C. J., Hagan, K. and Peltz, S. W. (1999) Mutations in VPS16 and MRTI stabilize mRNAs by activating an inhibitor of the decapping enzyme. Mol. Cell. BioL, 19: 7568–7576.

    PubMed  CAS  Google Scholar 

  50. Meacham, G. C., Browne, B. L., Zhang, W., Kellermayer, R., Bedwell, D. M. and Cyr, D. M. (1999) Mutations in the yeast Hsp40 chaperone protein Ydjl cause defects in Axll biogenesis and pro-a-factor processing. JBiol. Chem., 274: 34396–34402.

    Article  CAS  Google Scholar 

  51. Moseley, P. L., Wallen, E. S., McCafferty, J D., Flanagan, S and Kern, J. A. (1993) Heat stress regulates the human 70-kDa heat-shock gene through the 3’-untranslated region. Am. J. Physiol., 264: L533–537.

    PubMed  CAS  Google Scholar 

  52. Brennecke, T., Gellner, K. and Bosch, T. C. G. (1998) The lack of a stress response in Hydra oligactis is due to reduced hsp70 mRNA stability. Eur. J. Biochem., 255: 703709.

    Google Scholar 

  53. Lee, M. G-S. (1998) The 3’ untranslated region of the hsp 70 genes maintains the level of steady state mRNA in Trypanosoma brucei upon heat shock. Nucl. Acids Res., 26: 4025–4033.

    Article  PubMed  CAS  Google Scholar 

  54. Kaarniranta, K., Elo, M., Sironen, R., Lammi, M. J., Goldring, M. B., Erikson, J. E., Sistonen, L. and Helminen, H. J. (1998) Hsp70 accumulation in chondrocytic cells exposed to high continuous hydrostatic pressure coincides with mRNA stabilization rather than transcriptional activation. Proc. Natl. Acad. Sci., 95: 2319–2324.

    Article  PubMed  CAS  Google Scholar 

  55. Spicher, A., Guicherit, O. M., Duret, L., Aslanian, A., Sanjines, E. M., Denim, N. C., Giaccia, A. J. and Blau, H. M. (1998) Highly conserved RNA sequences that are sensors of environmental stress. Mol. Cell. Biol., 18: 7371–7382.

    PubMed  CAS  Google Scholar 

  56. Korber, P., Zander, T., Herschlag, D. and Bardwell, J. C. A. (1999) A new heat shock protein that binds nucleic acids. JBiol. Chem., 274: 249–256.

    Article  CAS  Google Scholar 

  57. Korber, P., Stahl, J. M., Nierhaus, K. H. and Bardwell, J. C. A. (2000) Hsp15: a ribosome-associated heat shock protein. EMBO J., 19: 741–748.

    Article  PubMed  CAS  Google Scholar 

  58. Staker, B. L., Korber, P., Bardwell, J. C. A. and Saper, M. (2000) Structure of Hsp15 reveals a novel RNA-binding motif. EMBO J., 19: 749–757.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer Science+Business Media New York

About this chapter

Cite this chapter

Zimmer, C., Nagy, E., Subjeck, J., Henics, T. (2002). RNA Binding by Members of the 70-kDa Family of Molecular Chaperones. In: Sandberg, K., Mulroney, S.E. (eds) RNA Binding Proteins. Endocrine Updates, vol 16. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-6446-8_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-6446-8_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-4935-6

  • Online ISBN: 978-1-4757-6446-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics