Letter | Published:

mRNA quality control is bypassed for immediate export of stress-responsive transcripts

Nature volume 540, pages 593596 (22 December 2016) | Download Citation


Cells grow well only in a narrow range of physiological conditions. Surviving extreme conditions requires the instantaneous expression of chaperones that help to overcome stressful situations. To ensure the preferential synthesis of these heat-shock proteins, cells inhibit transcription, pre-mRNA processing and nuclear export of non-heat-shock transcripts, while stress-specific mRNAs are exclusively exported and translated1. How cells manage the selective retention of regular transcripts and the simultaneous rapid export of heat-shock mRNAs is largely unknown. In Saccharomyces cerevisiae, the shuttling RNA adaptor proteins Npl3, Gbp2, Hrb1 and Nab2 are loaded co-transcriptionally onto growing pre-mRNAs. For nuclear export, they recruit the export-receptor heterodimer Mex67–Mtr2 (TAP–p15 in humans)2. Here we show that cellular stress induces the dissociation of Mex67 and its adaptor proteins from regular mRNAs to prevent general mRNA export. At the same time, heat-shock mRNAs are rapidly exported in association with Mex67, without the need for adapters. The immediate co-transcriptional loading of Mex67 onto heat-shock mRNAs involves Hsf1, a heat-shock transcription factor that binds to heat-shock-promoter elements in stress-responsive genes. An important difference between the export modes is that adaptor-protein-bound mRNAs undergo quality control, whereas stress-specific transcripts do not. In fact, regular mRNAs are converted into uncontrolled stress-responsive transcripts if expressed under the control of a heat-shock promoter, suggesting that whether an mRNA undergoes quality control is encrypted therein. Under normal conditions, Mex67 adaptor proteins are recruited for RNA surveillance, with only quality-controlled mRNAs allowed to associate with Mex67 and leave the nucleus. Thus, at the cost of error-free mRNA formation, heat-shock mRNAs are exported and translated without delay, allowing cells to survive extreme situations.

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We thank H. Bastians for advice, L. Oldehaver for technical assistance, W. Kramer for discussion and R. Lill, P. A. Silver, C. Dargemont and E. Hurt for providing plasmids, strains or antibodies. This work was funded by grants from the Deutsche Forschungsgemeinschaft and the SFB860 to H.K.

Author information

Author notes

    • Gesa Zander
    • , Alexandra Hackmann
    •  & Lysann Bender

    These authors contributed equally to this work


  1. Abteilung für Molekulare Genetik, Institut für Mikrobiologie und Genetik, Göttinger Zentrum für Molekulare Biowissenschaften, Georg-August Universität Göttingen, Göttingen, Germany

    • Gesa Zander
    • , Alexandra Hackmann
    • , Lysann Bender
    • , Daniel Becker
    •  & Heike Krebber
  2. Transkriptomanalyselabor, Institut für Entwicklungsbiochemie, Georg-August Universität Göttingen, Göttingen, Germany

    • Thomas Lingner
    •  & Gabriela Salinas


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Experiments were designed and data interpreted by all authors; experiments were performed by G.Z. (Figs 1b, c, 2d, e, 3c, 4b–d), A.H. (Figs 1c, 3a, b, 4a), L.B. (Figs 1a, 2a–c) D.B. (Fig. 1c) and T.L. and G.S. (Fig. 1c). The manuscript was written by H.K.; all authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Heike Krebber.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Methods for RIP-Microarray experiments and Supplementary Tables for Microarray.

  2. 2.

    Supplementary Information

    This file contains Supplementary Methods for RNA-Seq experiments and Supplementary Tables for RNA-sequencing.

  3. 3.

    Supplementary Information

    This file contains uncropped gel source data with size marker indications and Supplementary Figures 1-4.

Excel files

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    Supplementary Data

    This file contains raw data of the Microarray with functional groups for each gene, genes sorted for binding >0,5 log2 fold change for Mex67 and Npl3 at 42°C and 25°C and raw data for the total dissociation of mRNAs at 42°C.

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