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Edc3 Function in Yeast and Mammals Is Modulated by Interaction with NAD-Related Compounds

The control of mRNA translation and degradation is mediated in part by a set of proteins that can inhibit translation and promote decapping, as well as function in the assembly of cytoplasmic mRNP granules referred to as processing bodies (P-bodies). The conserved enhancer of mRNA decapping 3 (Edc3)...

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Autores principales: Walters, Robert W., Shumilin, Igor A., Yoon, Je-Hyun, Minor, Wladek, Parker, Roy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059234/
https://www.ncbi.nlm.nih.gov/pubmed/24504254
http://dx.doi.org/10.1534/g3.114.010470
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author Walters, Robert W.
Shumilin, Igor A.
Yoon, Je-Hyun
Minor, Wladek
Parker, Roy
author_facet Walters, Robert W.
Shumilin, Igor A.
Yoon, Je-Hyun
Minor, Wladek
Parker, Roy
author_sort Walters, Robert W.
collection PubMed
description The control of mRNA translation and degradation is mediated in part by a set of proteins that can inhibit translation and promote decapping, as well as function in the assembly of cytoplasmic mRNP granules referred to as processing bodies (P-bodies). The conserved enhancer of mRNA decapping 3 (Edc3) protein functions to promote both decapping and P-body assembly. Crystal structures of the YjeF_N domain in hEdc3 identified a putative binding site for a small molecule. Structure modeling of the human Edc3 Yjef_N along with other Yjef_N-containing proteins suggests that this molecule is related to NAD(H). We now show human Edc3 directly binds NADH. We also show that human and yeast Edc3 chemically modify NAD in vitro. Mutations that are predicted to disrupt the binding and/or hydrolysis of an NAD-related molecule by yeast and human Edc3 affect the control of mRNA degradation and/or P-body composition in vivo. This suggests that the interaction of Edc3 with an NAD-related molecule affects its function in the regulation of mRNA translation and degradation and provides a possible mechanism to couple the energetics of the cell to posttranscriptional control. Moreover, this provides a unique example of and lends strength to the postulated connection of metabolites, enzymes, and RNA.
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spelling pubmed-40592342014-06-16 Edc3 Function in Yeast and Mammals Is Modulated by Interaction with NAD-Related Compounds Walters, Robert W. Shumilin, Igor A. Yoon, Je-Hyun Minor, Wladek Parker, Roy G3 (Bethesda) Investigations The control of mRNA translation and degradation is mediated in part by a set of proteins that can inhibit translation and promote decapping, as well as function in the assembly of cytoplasmic mRNP granules referred to as processing bodies (P-bodies). The conserved enhancer of mRNA decapping 3 (Edc3) protein functions to promote both decapping and P-body assembly. Crystal structures of the YjeF_N domain in hEdc3 identified a putative binding site for a small molecule. Structure modeling of the human Edc3 Yjef_N along with other Yjef_N-containing proteins suggests that this molecule is related to NAD(H). We now show human Edc3 directly binds NADH. We also show that human and yeast Edc3 chemically modify NAD in vitro. Mutations that are predicted to disrupt the binding and/or hydrolysis of an NAD-related molecule by yeast and human Edc3 affect the control of mRNA degradation and/or P-body composition in vivo. This suggests that the interaction of Edc3 with an NAD-related molecule affects its function in the regulation of mRNA translation and degradation and provides a possible mechanism to couple the energetics of the cell to posttranscriptional control. Moreover, this provides a unique example of and lends strength to the postulated connection of metabolites, enzymes, and RNA. Genetics Society of America 2014-02-05 /pmc/articles/PMC4059234/ /pubmed/24504254 http://dx.doi.org/10.1534/g3.114.010470 Text en Copyright © 2014 Walters et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigations
Walters, Robert W.
Shumilin, Igor A.
Yoon, Je-Hyun
Minor, Wladek
Parker, Roy
Edc3 Function in Yeast and Mammals Is Modulated by Interaction with NAD-Related Compounds
title Edc3 Function in Yeast and Mammals Is Modulated by Interaction with NAD-Related Compounds
title_full Edc3 Function in Yeast and Mammals Is Modulated by Interaction with NAD-Related Compounds
title_fullStr Edc3 Function in Yeast and Mammals Is Modulated by Interaction with NAD-Related Compounds
title_full_unstemmed Edc3 Function in Yeast and Mammals Is Modulated by Interaction with NAD-Related Compounds
title_short Edc3 Function in Yeast and Mammals Is Modulated by Interaction with NAD-Related Compounds
title_sort edc3 function in yeast and mammals is modulated by interaction with nad-related compounds
topic Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059234/
https://www.ncbi.nlm.nih.gov/pubmed/24504254
http://dx.doi.org/10.1534/g3.114.010470
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