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RNA Specificity and Autoregulation of DDX17, a Modulator of MicroRNA Biogenesis

DDX17, a DEAD-box ATPase, is a multifunctional helicase important for various RNA functions, including microRNA maturation. Key questions for DDX17 include how it recognizes target RNAs and influences their structures, as well as how its ATPase activity may be regulated. Through crystal structures a...

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Detalles Bibliográficos
Autores principales: Ngo, Tri D., Partin, Alexander C., Nam, Yunsun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953907/
https://www.ncbi.nlm.nih.gov/pubmed/31851931
http://dx.doi.org/10.1016/j.celrep.2019.11.059
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author Ngo, Tri D.
Partin, Alexander C.
Nam, Yunsun
author_facet Ngo, Tri D.
Partin, Alexander C.
Nam, Yunsun
author_sort Ngo, Tri D.
collection PubMed
description DDX17, a DEAD-box ATPase, is a multifunctional helicase important for various RNA functions, including microRNA maturation. Key questions for DDX17 include how it recognizes target RNAs and influences their structures, as well as how its ATPase activity may be regulated. Through crystal structures and biochemical assays, we show the ability of the core catalytic domains of DDX17 to recognize specific sequences in target RNAs. The RNA sequence preference of the catalytic core is critical for DDX17 to directly bind and remodel a specific region of primary microRNAs 3′ to the mature sequence, and consequently enhance processing by Drosha. Furthermore, we identify an intramolecular interaction between the N-terminal tail and the DEAD domain of DDX17 to have an autoregulatory role in controlling the ATPase activity. Thus, we provide the molecular basis for how cognate RNA recognition and functional outcomes are linked for DDX17.
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spelling pubmed-69539072020-01-10 RNA Specificity and Autoregulation of DDX17, a Modulator of MicroRNA Biogenesis Ngo, Tri D. Partin, Alexander C. Nam, Yunsun Cell Rep Article DDX17, a DEAD-box ATPase, is a multifunctional helicase important for various RNA functions, including microRNA maturation. Key questions for DDX17 include how it recognizes target RNAs and influences their structures, as well as how its ATPase activity may be regulated. Through crystal structures and biochemical assays, we show the ability of the core catalytic domains of DDX17 to recognize specific sequences in target RNAs. The RNA sequence preference of the catalytic core is critical for DDX17 to directly bind and remodel a specific region of primary microRNAs 3′ to the mature sequence, and consequently enhance processing by Drosha. Furthermore, we identify an intramolecular interaction between the N-terminal tail and the DEAD domain of DDX17 to have an autoregulatory role in controlling the ATPase activity. Thus, we provide the molecular basis for how cognate RNA recognition and functional outcomes are linked for DDX17. 2019-12-17 /pmc/articles/PMC6953907/ /pubmed/31851931 http://dx.doi.org/10.1016/j.celrep.2019.11.059 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Ngo, Tri D.
Partin, Alexander C.
Nam, Yunsun
RNA Specificity and Autoregulation of DDX17, a Modulator of MicroRNA Biogenesis
title RNA Specificity and Autoregulation of DDX17, a Modulator of MicroRNA Biogenesis
title_full RNA Specificity and Autoregulation of DDX17, a Modulator of MicroRNA Biogenesis
title_fullStr RNA Specificity and Autoregulation of DDX17, a Modulator of MicroRNA Biogenesis
title_full_unstemmed RNA Specificity and Autoregulation of DDX17, a Modulator of MicroRNA Biogenesis
title_short RNA Specificity and Autoregulation of DDX17, a Modulator of MicroRNA Biogenesis
title_sort rna specificity and autoregulation of ddx17, a modulator of microrna biogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953907/
https://www.ncbi.nlm.nih.gov/pubmed/31851931
http://dx.doi.org/10.1016/j.celrep.2019.11.059
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