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DNA Template Dependent Accuracy Variation of Nucleotide Selection in Transcription
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 3, e0119588Article in journal (Refereed) Published
Abstract [en]

It has been commonly assumed that the effect of erroneous transcription of DNA genes into messenger RNAs on peptide sequence errors are masked by much more frequent errors of mRNA translation to protein. We present a theoretical model of transcriptional accuracy. It uses experimentally estimated standard free energies of double-stranded DNA and RNA/DNA hybrids and predicts a DNA template dependent transcriptional accuracy variation spanning several orders of magnitude. The model also identifies high-error as well a high-accuracy transcription motifs. The source of the large accuracy span is the context dependent variation of the stacking free energy of pairs of correct and incorrect base pairs in the ever moving transcription bubble. Our model predictions have direct experimental support from recent single molecule based identifications of transcriptional errors in the C. elegans transcriptome. Our conclusions challenge the general view that amino acid substitution errors in proteins are mainly caused by translational errors. It suggests instead that transcriptional error hotspots are the dominating source of peptide sequence errors in some DNA template contexts, while mRNA translation is the major cause of protein errors in other contexts.

Place, publisher, year, edition, pages
2015. Vol. 10, no 3, e0119588
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-252228DOI: 10.1371/journal.pone.0119588ISI: 000351987300062PubMedID: 25799551OAI: oai:DiVA.org:uu-252228DiVA: diva2:810055
Funder
VINNOVAWenner-Gren FoundationsKnut and Alice Wallenberg Foundation
Available from: 2015-05-06 Created: 2015-05-04 Last updated: 2017-12-04Bibliographically approved
In thesis
1. Speed and accuracy in transcription and translation: Modelling of transcript and polypeptide elongation
Open this publication in new window or tab >>Speed and accuracy in transcription and translation: Modelling of transcript and polypeptide elongation
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Uppsala Universitet, 2015
National Category
Biochemistry and Molecular Biology
Research subject
Biology with specialization in Molecular Biotechnology
Identifiers
urn:nbn:se:uu:diva-262698 (URN)
Public defence
2015-10-30, BMC A1:111a, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Funder
Knut and Alice Wallenberg FoundationVINNOVASwedish Research Council
Available from: 2015-10-08 Created: 2015-09-18 Last updated: 2015-11-23

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Mellenius, HarrietEhrenberg, Måns

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