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Characterization of the mammalian DEAD-box protein DDX5 reveals functional conservation with S. cerevisiae ortholog Dbp2 in transcriptional control and glucose metabolism

DEAD-box proteins are a class of nonprocessive RNA helicases that dynamically modulate the structure of RNA and ribonucleoprotein complexes (RNPs). However, the precise roles of individual members are not well understood. Work from our laboratory revealed that the DEAD-box protein Dbp2 in Saccharomy...

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Autores principales: Xing, Zheng, Wang, Siwen, Tran, Elizabeth J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473146/
https://www.ncbi.nlm.nih.gov/pubmed/28411202
http://dx.doi.org/10.1261/rna.060335.116
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author Xing, Zheng
Wang, Siwen
Tran, Elizabeth J.
author_facet Xing, Zheng
Wang, Siwen
Tran, Elizabeth J.
author_sort Xing, Zheng
collection PubMed
description DEAD-box proteins are a class of nonprocessive RNA helicases that dynamically modulate the structure of RNA and ribonucleoprotein complexes (RNPs). However, the precise roles of individual members are not well understood. Work from our laboratory revealed that the DEAD-box protein Dbp2 in Saccharomyces cerevisiae is an active RNA helicase in vitro that functions in transcription by promoting mRNP assembly, repressing cryptic transcription initiation, and regulating long noncoding RNA activity. Interestingly, Dbp2 is also linked to glucose sensing and hexose transporter gene expression. DDX5 is the mammalian ortholog of Dbp2 that has been implicated in cancer and metabolic syndrome, suggesting that the role of Dbp2 and DDX5 in glucose metabolic regulation is conserved. Herein, we present a refined biochemical and biological comparison of yeast Dbp2 and human DDX5 enzymes. We find that human DDX5 possesses a 10-fold higher unwinding activity than Dbp2, which is partially due to the presence of a mammalian/avian specific C-terminal extension. Interestingly, ectopic expression of DDX5 rescues the cold sensitivity, cryptic initiation defects, and impaired glucose import in dbp2Δ cells, suggesting functional conservation. Consistently, we show that DDX5 promotes glucose uptake and glycolysis in mouse AML12 hepatocyte cells, suggesting that mammalian DDX5 and S. cerevisiae Dbp2 share conserved roles in cellular metabolism.
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spelling pubmed-54731462018-07-01 Characterization of the mammalian DEAD-box protein DDX5 reveals functional conservation with S. cerevisiae ortholog Dbp2 in transcriptional control and glucose metabolism Xing, Zheng Wang, Siwen Tran, Elizabeth J. RNA Article DEAD-box proteins are a class of nonprocessive RNA helicases that dynamically modulate the structure of RNA and ribonucleoprotein complexes (RNPs). However, the precise roles of individual members are not well understood. Work from our laboratory revealed that the DEAD-box protein Dbp2 in Saccharomyces cerevisiae is an active RNA helicase in vitro that functions in transcription by promoting mRNP assembly, repressing cryptic transcription initiation, and regulating long noncoding RNA activity. Interestingly, Dbp2 is also linked to glucose sensing and hexose transporter gene expression. DDX5 is the mammalian ortholog of Dbp2 that has been implicated in cancer and metabolic syndrome, suggesting that the role of Dbp2 and DDX5 in glucose metabolic regulation is conserved. Herein, we present a refined biochemical and biological comparison of yeast Dbp2 and human DDX5 enzymes. We find that human DDX5 possesses a 10-fold higher unwinding activity than Dbp2, which is partially due to the presence of a mammalian/avian specific C-terminal extension. Interestingly, ectopic expression of DDX5 rescues the cold sensitivity, cryptic initiation defects, and impaired glucose import in dbp2Δ cells, suggesting functional conservation. Consistently, we show that DDX5 promotes glucose uptake and glycolysis in mouse AML12 hepatocyte cells, suggesting that mammalian DDX5 and S. cerevisiae Dbp2 share conserved roles in cellular metabolism. Cold Spring Harbor Laboratory Press 2017-07 /pmc/articles/PMC5473146/ /pubmed/28411202 http://dx.doi.org/10.1261/rna.060335.116 Text en © 2017 Xing et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Article
Xing, Zheng
Wang, Siwen
Tran, Elizabeth J.
Characterization of the mammalian DEAD-box protein DDX5 reveals functional conservation with S. cerevisiae ortholog Dbp2 in transcriptional control and glucose metabolism
title Characterization of the mammalian DEAD-box protein DDX5 reveals functional conservation with S. cerevisiae ortholog Dbp2 in transcriptional control and glucose metabolism
title_full Characterization of the mammalian DEAD-box protein DDX5 reveals functional conservation with S. cerevisiae ortholog Dbp2 in transcriptional control and glucose metabolism
title_fullStr Characterization of the mammalian DEAD-box protein DDX5 reveals functional conservation with S. cerevisiae ortholog Dbp2 in transcriptional control and glucose metabolism
title_full_unstemmed Characterization of the mammalian DEAD-box protein DDX5 reveals functional conservation with S. cerevisiae ortholog Dbp2 in transcriptional control and glucose metabolism
title_short Characterization of the mammalian DEAD-box protein DDX5 reveals functional conservation with S. cerevisiae ortholog Dbp2 in transcriptional control and glucose metabolism
title_sort characterization of the mammalian dead-box protein ddx5 reveals functional conservation with s. cerevisiae ortholog dbp2 in transcriptional control and glucose metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473146/
https://www.ncbi.nlm.nih.gov/pubmed/28411202
http://dx.doi.org/10.1261/rna.060335.116
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AT wangsiwen characterizationofthemammaliandeadboxproteinddx5revealsfunctionalconservationwithscerevisiaeorthologdbp2intranscriptionalcontrolandglucosemetabolism
AT tranelizabethj characterizationofthemammaliandeadboxproteinddx5revealsfunctionalconservationwithscerevisiaeorthologdbp2intranscriptionalcontrolandglucosemetabolism