University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Microbiology and Physiological Systems

Publication Date

5-24-2018

Document Type

Article Preprint

Disciplines

Amino Acids, Peptides, and Proteins | Biochemistry | Nucleic Acids, Nucleotides, and Nucleosides

Abstract

Nonsense suppressors (NonSups) treat premature termination codon (PTC) disorders by inducing the selection of near cognate tRNAs at the PTC position, allowing readthrough of the PTC and production of full-length protein. Studies of NonSup-induced readthrough of eukaryotic PTCs have been carried out using animals, cells or crude cell extracts. In these studies, NonSups can promote readthrough directly, by binding to components of the protein synthesis machinery, or indirectly, by inhibiting nonsense-mediated mRNA decay or by other mechanisms. Here we utilize a highly-purified in vitro system (Zhang et al., 2016. eLife 5: e13429) to measure exclusively direct NonSup-induced readthrough. Of 17 previously identified NonSups, 13 display direct effects, apparently via at least two different mechanisms. We can monitor such direct effects by single molecule FRET (smFRET). Future smFRET experiments will permit elucidation of the mechanisms by which NonSups stimulate direct readthrough, aiding ongoing efforts to improve the clinical usefulness of NonSups.

Keywords

nonsense suppressors, eukaryotic protein synthesis machinery, single molecule FRET, biochemistry

Rights and Permissions

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY 4.0 International license.

DOI of Published Version

10.1101/330506

Source

bioRxiv 330506; doi: https://doi.org/10.1101/330506. Link to preprint on bioRxiv service.

Journal/Book/Conference Title

bioRxiv

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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