The landscape of transcription errors in eukaryotic cells

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Science Advances  20 Oct 2017:
Vol. 3, no. 10, e1701484
DOI: 10.1126/sciadv.1701484

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  • Biological Significance of Transcription Errors
    • Bert M. Verheijen, Laboratory of Experimental Neurology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
    • Other Contributors:
      • Fred W. van Leeuwen, Department of Neuroscience, Maastricht University, Maastricht, The Netherlands

    We read with great interest the article by J.-F. Gout et al. on the analysis of transcription errors in yeast (“The landscape of transcription errors in eukaryotic cells”, published online 20 October 2017). This study provides a particularly detailed examination of erroneous transcription using a “circle-sequencing” method, which was first described by Acevedo et al. (1, 2). The data confirms that transcriptional error rates and distribution of errors are intrinsic properties of RNA polymerases.

    The phenotypic effects of transcriptional infidelity in cells remain largely unknown. The authors attempted to find out more about these effects through the analysis of error-prone RNA polymerase mutants. Increased transcription error rates were found to induce proteotoxic stress, which is compatible with earlier observations (3). Gene mutations (4) and translation errors (5) were previously shown to have similar effects on protein folding and could explain a tendency of erroneous transcripts to affect the structural integrity of proteins.

    Interestingly, alterations in several other cellular pathways (related to nitrogen metabolism, nucleotide availability and NAD stocks) were observed in the error-prone cells. The authors speculate that these could reflect specific biological alterations (e.g., depletion due to increased RNA and protein turnover, reduced cellular lifespan), but they do not provide a mechanistic explanation for these changes, which is a weakness of...

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    Competing Interests: None declared.

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