A fluorescence-based assay suitable for quantitative analysis of deadenylase enzyme activity

In eukaryotic cells, the shortening and removal of the poly(A) tail of cytoplasmic mRNA by deadenylase enzymes is a critical step in posttranscriptional gene regulation. The ribonuclease activity of deadenylase enzymes is attributed to either a DEDD (Asp-Glu-Asp-Asp) or an endonuclease–exonuclease–...

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Main Authors: Maryati, Marayti, Kaur, Ishwinder, Jadhav, Gopal P., Olotu-Umoren, Loyin, Oveh, Blessing, Hashmi, Lubna, Fischer, Peter M., Winkler, G. Sebastiaan
Format: Article
Published: Oxford Journals 2013
Online Access:https://eprints.nottingham.ac.uk/2323/
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author Maryati, Marayti
Kaur, Ishwinder
Jadhav, Gopal P.
Olotu-Umoren, Loyin
Oveh, Blessing
Hashmi, Lubna
Fischer, Peter M.
Winkler, G. Sebastiaan
author_facet Maryati, Marayti
Kaur, Ishwinder
Jadhav, Gopal P.
Olotu-Umoren, Loyin
Oveh, Blessing
Hashmi, Lubna
Fischer, Peter M.
Winkler, G. Sebastiaan
author_sort Maryati, Marayti
building Nottingham Research Data Repository
collection Online Access
description In eukaryotic cells, the shortening and removal of the poly(A) tail of cytoplasmic mRNA by deadenylase enzymes is a critical step in posttranscriptional gene regulation. The ribonuclease activity of deadenylase enzymes is attributed to either a DEDD (Asp-Glu-Asp-Asp) or an endonuclease–exonuclease–phosphatase domain. Both domains require the presence of two Mg2+ ions in the active site. To facilitate the biochemical analysis of deadenylase enzymes, we have developed a fluorescence-based deadenylase assay. The assay is based on end-point measurement, suitable for quantitative analysis and can be adapted for 96- and 384-well microplate formats. We demonstrate the utility of the assay by screening a chemical compound library, resulting in the identification of non-nucleoside inhibitors of the Caf1/CNOT7 enzyme, a catalytic subunit of the Ccr4–Not deadenylase complex. These compounds may be useful tools for the biochemical analysis of the Caf1/CNOT7 deadenylase subunit of the Ccr4–Not complex and indicate the feasibility of developing selective inhibitors of deadenylase enzymes using the fluorescencebased assay.
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spelling nottingham-23232020-05-04T16:39:09Z https://eprints.nottingham.ac.uk/2323/ A fluorescence-based assay suitable for quantitative analysis of deadenylase enzyme activity Maryati, Marayti Kaur, Ishwinder Jadhav, Gopal P. Olotu-Umoren, Loyin Oveh, Blessing Hashmi, Lubna Fischer, Peter M. Winkler, G. Sebastiaan In eukaryotic cells, the shortening and removal of the poly(A) tail of cytoplasmic mRNA by deadenylase enzymes is a critical step in posttranscriptional gene regulation. The ribonuclease activity of deadenylase enzymes is attributed to either a DEDD (Asp-Glu-Asp-Asp) or an endonuclease–exonuclease–phosphatase domain. Both domains require the presence of two Mg2+ ions in the active site. To facilitate the biochemical analysis of deadenylase enzymes, we have developed a fluorescence-based deadenylase assay. The assay is based on end-point measurement, suitable for quantitative analysis and can be adapted for 96- and 384-well microplate formats. We demonstrate the utility of the assay by screening a chemical compound library, resulting in the identification of non-nucleoside inhibitors of the Caf1/CNOT7 enzyme, a catalytic subunit of the Ccr4–Not deadenylase complex. These compounds may be useful tools for the biochemical analysis of the Caf1/CNOT7 deadenylase subunit of the Ccr4–Not complex and indicate the feasibility of developing selective inhibitors of deadenylase enzymes using the fluorescencebased assay. Oxford Journals 2013-10-28 Article PeerReviewed Maryati, Marayti, Kaur, Ishwinder, Jadhav, Gopal P., Olotu-Umoren, Loyin, Oveh, Blessing, Hashmi, Lubna, Fischer, Peter M. and Winkler, G. Sebastiaan (2013) A fluorescence-based assay suitable for quantitative analysis of deadenylase enzyme activity. Nucleic Acids Research . pp. 1-10. ISSN 0305-1048 http://nar.oxfordjournals.org/content/early/2013/10/28/nar.gkt972.full doi:10.1093/nar/gkt972 doi:10.1093/nar/gkt972
spellingShingle Maryati, Marayti
Kaur, Ishwinder
Jadhav, Gopal P.
Olotu-Umoren, Loyin
Oveh, Blessing
Hashmi, Lubna
Fischer, Peter M.
Winkler, G. Sebastiaan
A fluorescence-based assay suitable for quantitative analysis of deadenylase enzyme activity
title A fluorescence-based assay suitable for quantitative analysis of deadenylase enzyme activity
title_full A fluorescence-based assay suitable for quantitative analysis of deadenylase enzyme activity
title_fullStr A fluorescence-based assay suitable for quantitative analysis of deadenylase enzyme activity
title_full_unstemmed A fluorescence-based assay suitable for quantitative analysis of deadenylase enzyme activity
title_short A fluorescence-based assay suitable for quantitative analysis of deadenylase enzyme activity
title_sort fluorescence-based assay suitable for quantitative analysis of deadenylase enzyme activity
url https://eprints.nottingham.ac.uk/2323/
https://eprints.nottingham.ac.uk/2323/
https://eprints.nottingham.ac.uk/2323/