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Messenger RNA targeting to endoplasmic reticulum stress signalling sites

Author

Listed:
  • Tomás Aragón

    (and
    Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94158-2517, USA)

  • Eelco van Anken

    (and
    Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94158-2517, USA)

  • David Pincus

    (and
    Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94158-2517, USA)

  • Iana M. Serafimova

    (and
    Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94158-2517, USA)

  • Alexei V. Korennykh

    (and
    Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94158-2517, USA)

  • Claudia A. Rubio

    (and
    Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94158-2517, USA)

  • Peter Walter

    (and
    Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94158-2517, USA)

Abstract

The unfolding story The accumulation of misfolded proteins activates the unfolded protein response in the endoplasmic reticulum. The transmembrane protein Ire1 is a central player in this pathway, acting as a kinase and an endoribonuclease. It excises an intron on HAC1 mRNA resulting in translation of the transcription factor Hac1 that in turn activates target genes. This issue reports two studies on Ire1. Korennykh et al. solve the crystal structure of Ire1 kinase and show that it spontaneously assembles into a rod-shaped oligomer. This positions the kinase domains for trans-phosphorylation, orders the RNase domains and creates an interaction site for mRNA substrate binding. Aragón et al. show that on activation, Ire1 molecules cluster into discrete foci containing high-order oligomers on the endoplasmic reticulum membrane. HAC1 mRNA is recruited to these foci by means of a sequence in its 3′ untranslated region and is processed at these sites. In this way the HAC1 mRNA is delivered to a site where it is processed, ensuring that it is translated only when the unfolded protein response is on.

Suggested Citation

  • Tomás Aragón & Eelco van Anken & David Pincus & Iana M. Serafimova & Alexei V. Korennykh & Claudia A. Rubio & Peter Walter, 2009. "Messenger RNA targeting to endoplasmic reticulum stress signalling sites," Nature, Nature, vol. 457(7230), pages 736-740, February.
    • Handle: RePEc:nat:nature:v:457:y:2009:i:7230:d:10.1038_nature07641
    DOI: 10.1038/nature07641
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